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Alterations in Skeletal Muscle Microvascular Hematocrit with Short-Term Reduced Renal Mass Hypertension
Microvascular Research 59, 390 –393 (2000) doi:10.1006/mvre.1999.2235, available online at http://www.idealibrary.com on
BRIEF COMMUNICATION Alterations in Skeletal Muscle Microvascular Hematocrit with Short-Term Reduced Renal Mass Hypertension Jefferson C. Frisbee and Julian H. Lombard Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226 Received December 2, 1999
INTRODUCTION Previous studies in our laboratory have demonstrated that both short-term ingestion of high salt diet in normotensive animals and short-term reduced renal mass hypertension (RRMHT) alter the reactivity of rat skeletal muscle arterioles to vasoactive agonists acting at various points in the signal transduction pathways of vascular tone regulation (Frisbee and Lombard, 1999a,b). In addition, Hansen-Smith et al. (1996) determined that both short-term high salt diet and RRMHT reduce microvessel density in rat skeletal muscle (microvessel rarefaction), an alteration that had previously been thought to develop over a longer time frame. However, one key issue that has yet to be addressed in addition to the altered structure and reactivity of skeletal muscle microvessels during short-term high salt diet and RRMHT is the effect on microvascular hematocrit as a result of these conditions. Using a mathematical model of the hamster cheek pouch microcirculation, Greene et al. (1989) predicted that microvessel rarefaction increases the blood flow heterogeneity within microvascular networks. This effect should lead to a reduction in microvascular he-
390
matocrit, manifested through an enhanced nonuniform distribution of erythrocytes at microvessel bifurcations (Cokelet, 1982; Pries et al., 1986). Previous studies have suggested that a reduction in microvascular hematocrit can have significant ramifications for tissue oxygenation (Bos et al., 1995), which may help to explain existing observations of a more rapid development of muscle fatigue in rats with RRMHT (O’Drobinak et al., 1996). The present study tested the hypothesis that the structural and functional alterations occurring to the microcirculation in rats with RRMHT and in normotensive rats on high salt diet lead to a reduction in microvascular hematocrit.
MATERIALS AND METHODS Animal groups. Male Sprague–Dawley rats were anesthetized with a 9:2 mixture of 100 mg 䡠 ml ⫺1 ketamine and 10 mg 䡠 ml ⫺1 acepromazine (0.1 ml 䡠 100 g ⫺1 body wt). Total renal mass was reduced by approximately 75% utilizing a two-stage surgical procedure that has been described previously (Lombard et al., 1989). After recovery from the procedures, all rats 0026-2862/00 $35.00 Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.
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Brief Communication
with reduced renal mass were placed on high salt diet (4.0% NaCl; Dyets, Bethlehem, PA) for 3 days to produce RRM-hypertension (n ⫽ 9; MAP ⫽ 154 ⫾ 4.2 mm Hg). Two groups of normotensive sham-operated controls were prepared and maintained on either high salt (n ⫽ 8; MAP ⫽ 128 ⫾ 5.3 mm Hg) or low salt diet (0.4% NaCl; n ⫽ 10; MAP ⫽ 125 ⫾ 3.4 mm Hg) for an equivalent time. Experiment procedure and data analyses. On the day of the experiment, rats were anesthetized with sodium pentobarbital (60 mg 䡠 kg ⫺1, ip). The trachea was cannulated to insure a patent airway and a carotid artery and femoral vein were cannulated for measurement of arterial pressure and administration of supplemental anesthetic, respectively. After the initial surgery was complete, the right cremaster muscle was prepared for television microscopy (Lombard et al., 1989) and continuously superfused with physiological salt solution (PSS) equilibrated with a 5% CO 2/95% N 2 gas mixture to insure that oxygen delivery to the tissue was from the microcirculation and not from the superfusion solution. The PSS used in these experiments had the following ionic composition (mM): NaCl 130; KCl 4.7; CaCl 2 1.6; NaH 2PO 4 1.18; MgSO 4 1.17; NaHCO 3 14.9; and disodium EDTA 0.026. Succinylcholine chloride (0.1 mM) was added to the superfusion solution to prevent spontaneous contractions of the cremaster muscle. For determination of capillary erythrocyte velocity, videotapes were made utilizing a 436-nm bandpass filter to enhance the contrast between red blood cells (RBC) and the background. RBC velocities were measured from the videotapes by cross correlation in the frequency domain using the dual window technique, as previously described (Fenoy and Roman, 1991). Each measurement of RBC velocity in an individual capillary was the mean of five 17-s sampling intervals. Microvascular hematocrit (H MV) was determined by counting the number of erythrocytes within a measured capillary segment from still frames of the video record. Final H MV measures represent the mean of multiple determinations made during these periods. The calculation of H MV used the equation (Desjardins and Duling, 1987) H MV ⫽ 共n 䡠 MCV 䡠 100兲/关 䡠 共D/2兲 2 䡠 L兴,
FIG. 1. Capillary erythrocyte velocity in the cremaster muscle of RRM-hypertensive rats and normotensive rats on low or high salt diet during resting conditions (PSS, left) and during maximal dilation with 10 ⫺4 M adenosine (right). Data are summarized as means ⫾ SEM. Parentheses indicate the number of measurements in 8 –10 animals per group. Asterisks denote significant difference (P ⬍ 0.05) from normotensive rats on low salt diet. Dagger denotes significant difference (P ⬍ 0.05) from normotensive rats on high salt diet.
where n represents the number of erythrocytes in a given length of capillary (L), and MCV and D represent mean corpuscular volume (72 m 3) and capillary diameter (6.7 m), respectively (House and Lipowsky, 1987). After an initial equilibration period, variables were measured during resting conditions and during maximal dilation of the microcirculation produced by superfusing the cremaster muscle with PSS containing 10 ⫺4 M adenosine. Statistical analyses. Data are presented as means ⫾ SEM. Differences between groups were determined using analysis of variance followed by Tukey’s test, post hoc. A probability of P ⬍ 0.05 was considered statistically significant.
RESULTS Figure 1 summarizes capillary erythrocyte velocity in the cremaster muscle of normotensive rats on low salt or high salt diet and in RRM-hypertensive rats. During superfusion with normal PSS, capillary RBC velocity was higher in normotensive rats on high salt
Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.
392
FIG. 2. Capillary hematocrit in the cremaster muscle of normotensive rats on low salt or high salt diet and in RRM-hypertensive rats during resting conditions (PSS, left) and during maximal dilation with 10 ⫺4 M adenosine (right). Data are summarized as means ⫾ SEM. Parentheses indicate the number of measurements in 8 –10 animals per group. Asterisk denotes significant difference (P ⬍ 0.05) from normotensive rats on low salt diet. Dagger denotes significant difference (P ⬍ 0.05) from normotensive rats on high salt diet.
diet compared to rats on low salt diet. In RRM-hypertensive rats, RBC velocity was significantly higher than that in either of the normotensive rat groups, regardless of dietary salt level. These differences were abolished during maximal dilation of the cremaster muscle microcirculation by superfusion with 10 ⫺4 M adenosine, as capillary RBC velocity under these conditions was not different between the animal groups. Data describing the microvascular hematocrit in cremaster muscles of the three rat groups under resting conditions and during maximal dilation are summarized in Fig. 2. Under resting conditions, H MV was not different between normotensive rats on either low or high salt diet, although H MV in RRM-hypertensive rats was significantly less than that in either normotensive group. These differences were eliminated with maximum vasodilation, as H MV during superfusion with adenosine was not different among the three animal groups.
DISCUSSION Previous studies in our laboratory have demonstrated that short-term high salt diet and RRM-hyper-
Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.
Brief Communication
tension result in severe alterations in the structure and reactivity of skeletal muscle microvessels. These include rarefaction of microvessels smaller than 20 m in diameter (Hansen-Smith et al., 1996) and impaired relaxation of arterioles in response to a wide array of vasodilator stimuli (Frisbee and Lombard, 1999a,b). However, it remains to be determined whether these alterations to the skeletal muscle microcirculation with high salt diet and volume-expanded hypertension alter the characteristics of blood flow within capillaries. If altered mechanisms of vascular tone regulation act in concert with microvessel rarefaction leading to a reduction in H MV, the normal patterns of skeletal muscle oxygenation (Greene et al., 1992; Bos et al., 1995) could be radically altered, contributing to the increased rate of muscle fatigue that has been reported in RRM-hypertensive rats (O’Drobinak and Greene, 1996). Previous studies have determined that erythrocyte velocity within the microcirculation of spontaneously hypertensive rats is higher than that in normotensive animals (Henrich and Hertel, 1979). The present study demonstrates that capillary erythrocyte velocity during resting conditions is also higher in RRM-hypertensive rats (and normotensive rats on high salt diet) than in normotensive rats on low salt diet. However, no differences were evident between groups during maximal dilation of the cremasteric microcirculation with adenosine. The range of values for H MV in the present study corresponds well with previous studies in rat cremaster muscle (House and Lipowsky, 1987) and in the hamster cremaster muscle preparations (Desjardins and Duling, 1987), studies from which the methods employed in the present experiments for determining H MV were taken. The results of this study clearly demonstrate that, under resting conditions, H MV is reduced in the cremaster muscle of rats with acute RRM-hypertension, but not in normotensive rats on high salt diet. However, H MV in the maximally dilated microcirculation was not different between the experimental groups. To our knowledge, the results from the present study represent the first observations addressing the effects of volume-expanded hypertension on skeletal muscle H MV and clearly indicate that this variable is reduced under this condition.
393
Brief Communication
Previous studies suggest a possible mechanism through which H MV is reduced in RRM-hypertensive rats. Mathematical modeling studies have predicted that the microvessel rarefaction that has been demonstrated with acute RRM-hypertension (Hansen-Smith et al., 1996) will increase blood flow heterogeneity within microvascular networks (Greene et al., 1989). This increased flow heterogeneity at microvessel bifurcations will reduce mean microvascular hematocrit as a result of an enhanced manifestation of the network Fahraeus effect (Pries et al., 1986; Cokelet, 1982). In addition, the increased capillary erythrocyte velocity will, by definition, decrease hematocrit within an individual capillary owing to the vessel Fahraeus effect (Pries et al., 1986; Cokelet, 1982). Under conditions of maximal dilation, H MV was not different among the three rat groups. If the discussion in the preceding paragraph regarding the effects of microvessel density on H MV is accurate, these observations suggest that the rapid microvessel rarefaction with RRM-hypertension may be predominantly “functional” in nature, where some microvessels are unperfused under resting conditions. Subsequent addition of potent vasodilator stimuli (e.g., 10 ⫺4 M adenosine) would open microvessels that were “functionally rarefied” in RRM-hypertensive rats, restoring perfusion of the microvascular network to levels comparable to those in normotensive rats. Clearly, the results of these experiments indicate that further investigation of the alterations in microvascular hemodynamics and tissue oxygenation with high salt diet and RRM-hypertension is warranted.
ACKNOWLEDGMENTS The present experiments were supported by NIH Grants HL37374 and HL29587.
REFERENCES Bos, C., Hoofd, L., and Oostendorp, T. (1995). Mathematical model of erythrocytes as point-like sources. Math. Biosci. 125, 165–189. Cokelet, G. R. (1982). Speculation on the cause of low vessel hematocrits in the microcirculation. Microcirculation 2, 1–18. Desjardins, C., and Duling, B. R. (1987). Microvessel hematocrit: Measurement and implications for capillary oxygen transport. Am. J. Physiol. 252, H494 –H503. Fenoy, F. J., and Roman, R. J. (1991). Effect of volume expansion on papillary blood flow and sodium excretion. Am. J. Physiol. 260, F813–F822. Frisbee, J. C., and Lombard, J. H. (1999a). Acute elevations in salt intake and reduced renal mass hypertension compromise arteriolar dilation in rat cremaster muscle. Microvasc. Res. 57, 273–283. Frisbee, J. C., and Lombard, J. H. (1999b). Development and reversibility of altered skeletal muscle arteriolar structure and reactivity with high salt diet and reduced renal mass hypertension. Microcirculation 6, 215–225. Greene, A. S., Tonellato, P. J., Zhang, Z., Lombard, J. H., and Cowley, A. W., Jr. (1992). Effect of microvascular rarefaction on tissue oxygen delivery in hypertension. Am. J. Physiol. 262, H1486 –H1493. Greene, A. S., Tonellato, P. J., Lui, J., Lombard, J. H., and Cowley, A. W., Jr. (1989). Microvascular rarefaction and tissue vascular resistance in hypertension. Am. J. Physiol. 256, H126 –H131. Hansen-Smith, F. M., Morris, L. W., Greene, A. S., and Lombard, J. H. (1996). Rapid microvessel rarefaction with elevated salt intake and reduced renal mass hypertension in rats. Circ. Res. 79, 324 –330. Henrich, H., and Hertel, R. (1979). Hemodynamics and “rarification” of the microvasculature in spontaneously hypertensive rats. Bibl. Anat. 18, 184 –186. House, S. D., and Lipowsky, H. H. (1987). Microvascular hematocrit and red cell flux in rat cremaster muscle. Am. J. Physiol. 252, H211–H222. Lombard, J. H., Hinojosa-Laborde, C., and Cowley, A. W., Jr. (1989). Hemodynamics and microcirculatory alterations in reduced renal mass hypertension. Hypertension 13, 128 –138. O’Drobinak, D. M., and Greene, A. S. (1996). Decreases in steadystate muscle performance and vessel density in reduced renal mass hypertensive rats. Am. J. Physiol. 270, H661–H667. Pries, A. R., Ley, K., and Gaehtgens, P. (1986). Generalization of the Fahraeus principle for microvessel networks. Am. J. Physiol. 251, H1324 –1332.
Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.
BRIEF COMMUNICATION Alterations in Skeletal Muscle Microvascular Hematocrit with Short-Term Reduced Renal Mass Hypertension Jefferson C. Frisbee and Julian H. Lombard Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226 Received December 2, 1999
INTRODUCTION Previous studies in our laboratory have demonstrated that both short-term ingestion of high salt diet in normotensive animals and short-term reduced renal mass hypertension (RRMHT) alter the reactivity of rat skeletal muscle arterioles to vasoactive agonists acting at various points in the signal transduction pathways of vascular tone regulation (Frisbee and Lombard, 1999a,b). In addition, Hansen-Smith et al. (1996) determined that both short-term high salt diet and RRMHT reduce microvessel density in rat skeletal muscle (microvessel rarefaction), an alteration that had previously been thought to develop over a longer time frame. However, one key issue that has yet to be addressed in addition to the altered structure and reactivity of skeletal muscle microvessels during short-term high salt diet and RRMHT is the effect on microvascular hematocrit as a result of these conditions. Using a mathematical model of the hamster cheek pouch microcirculation, Greene et al. (1989) predicted that microvessel rarefaction increases the blood flow heterogeneity within microvascular networks. This effect should lead to a reduction in microvascular he-
390
matocrit, manifested through an enhanced nonuniform distribution of erythrocytes at microvessel bifurcations (Cokelet, 1982; Pries et al., 1986). Previous studies have suggested that a reduction in microvascular hematocrit can have significant ramifications for tissue oxygenation (Bos et al., 1995), which may help to explain existing observations of a more rapid development of muscle fatigue in rats with RRMHT (O’Drobinak et al., 1996). The present study tested the hypothesis that the structural and functional alterations occurring to the microcirculation in rats with RRMHT and in normotensive rats on high salt diet lead to a reduction in microvascular hematocrit.
MATERIALS AND METHODS Animal groups. Male Sprague–Dawley rats were anesthetized with a 9:2 mixture of 100 mg 䡠 ml ⫺1 ketamine and 10 mg 䡠 ml ⫺1 acepromazine (0.1 ml 䡠 100 g ⫺1 body wt). Total renal mass was reduced by approximately 75% utilizing a two-stage surgical procedure that has been described previously (Lombard et al., 1989). After recovery from the procedures, all rats 0026-2862/00 $35.00 Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.
391
Brief Communication
with reduced renal mass were placed on high salt diet (4.0% NaCl; Dyets, Bethlehem, PA) for 3 days to produce RRM-hypertension (n ⫽ 9; MAP ⫽ 154 ⫾ 4.2 mm Hg). Two groups of normotensive sham-operated controls were prepared and maintained on either high salt (n ⫽ 8; MAP ⫽ 128 ⫾ 5.3 mm Hg) or low salt diet (0.4% NaCl; n ⫽ 10; MAP ⫽ 125 ⫾ 3.4 mm Hg) for an equivalent time. Experiment procedure and data analyses. On the day of the experiment, rats were anesthetized with sodium pentobarbital (60 mg 䡠 kg ⫺1, ip). The trachea was cannulated to insure a patent airway and a carotid artery and femoral vein were cannulated for measurement of arterial pressure and administration of supplemental anesthetic, respectively. After the initial surgery was complete, the right cremaster muscle was prepared for television microscopy (Lombard et al., 1989) and continuously superfused with physiological salt solution (PSS) equilibrated with a 5% CO 2/95% N 2 gas mixture to insure that oxygen delivery to the tissue was from the microcirculation and not from the superfusion solution. The PSS used in these experiments had the following ionic composition (mM): NaCl 130; KCl 4.7; CaCl 2 1.6; NaH 2PO 4 1.18; MgSO 4 1.17; NaHCO 3 14.9; and disodium EDTA 0.026. Succinylcholine chloride (0.1 mM) was added to the superfusion solution to prevent spontaneous contractions of the cremaster muscle. For determination of capillary erythrocyte velocity, videotapes were made utilizing a 436-nm bandpass filter to enhance the contrast between red blood cells (RBC) and the background. RBC velocities were measured from the videotapes by cross correlation in the frequency domain using the dual window technique, as previously described (Fenoy and Roman, 1991). Each measurement of RBC velocity in an individual capillary was the mean of five 17-s sampling intervals. Microvascular hematocrit (H MV) was determined by counting the number of erythrocytes within a measured capillary segment from still frames of the video record. Final H MV measures represent the mean of multiple determinations made during these periods. The calculation of H MV used the equation (Desjardins and Duling, 1987) H MV ⫽ 共n 䡠 MCV 䡠 100兲/关 䡠 共D/2兲 2 䡠 L兴,
FIG. 1. Capillary erythrocyte velocity in the cremaster muscle of RRM-hypertensive rats and normotensive rats on low or high salt diet during resting conditions (PSS, left) and during maximal dilation with 10 ⫺4 M adenosine (right). Data are summarized as means ⫾ SEM. Parentheses indicate the number of measurements in 8 –10 animals per group. Asterisks denote significant difference (P ⬍ 0.05) from normotensive rats on low salt diet. Dagger denotes significant difference (P ⬍ 0.05) from normotensive rats on high salt diet.
where n represents the number of erythrocytes in a given length of capillary (L), and MCV and D represent mean corpuscular volume (72 m 3) and capillary diameter (6.7 m), respectively (House and Lipowsky, 1987). After an initial equilibration period, variables were measured during resting conditions and during maximal dilation of the microcirculation produced by superfusing the cremaster muscle with PSS containing 10 ⫺4 M adenosine. Statistical analyses. Data are presented as means ⫾ SEM. Differences between groups were determined using analysis of variance followed by Tukey’s test, post hoc. A probability of P ⬍ 0.05 was considered statistically significant.
RESULTS Figure 1 summarizes capillary erythrocyte velocity in the cremaster muscle of normotensive rats on low salt or high salt diet and in RRM-hypertensive rats. During superfusion with normal PSS, capillary RBC velocity was higher in normotensive rats on high salt
Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.
392
FIG. 2. Capillary hematocrit in the cremaster muscle of normotensive rats on low salt or high salt diet and in RRM-hypertensive rats during resting conditions (PSS, left) and during maximal dilation with 10 ⫺4 M adenosine (right). Data are summarized as means ⫾ SEM. Parentheses indicate the number of measurements in 8 –10 animals per group. Asterisk denotes significant difference (P ⬍ 0.05) from normotensive rats on low salt diet. Dagger denotes significant difference (P ⬍ 0.05) from normotensive rats on high salt diet.
diet compared to rats on low salt diet. In RRM-hypertensive rats, RBC velocity was significantly higher than that in either of the normotensive rat groups, regardless of dietary salt level. These differences were abolished during maximal dilation of the cremaster muscle microcirculation by superfusion with 10 ⫺4 M adenosine, as capillary RBC velocity under these conditions was not different between the animal groups. Data describing the microvascular hematocrit in cremaster muscles of the three rat groups under resting conditions and during maximal dilation are summarized in Fig. 2. Under resting conditions, H MV was not different between normotensive rats on either low or high salt diet, although H MV in RRM-hypertensive rats was significantly less than that in either normotensive group. These differences were eliminated with maximum vasodilation, as H MV during superfusion with adenosine was not different among the three animal groups.
DISCUSSION Previous studies in our laboratory have demonstrated that short-term high salt diet and RRM-hyper-
Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.
Brief Communication
tension result in severe alterations in the structure and reactivity of skeletal muscle microvessels. These include rarefaction of microvessels smaller than 20 m in diameter (Hansen-Smith et al., 1996) and impaired relaxation of arterioles in response to a wide array of vasodilator stimuli (Frisbee and Lombard, 1999a,b). However, it remains to be determined whether these alterations to the skeletal muscle microcirculation with high salt diet and volume-expanded hypertension alter the characteristics of blood flow within capillaries. If altered mechanisms of vascular tone regulation act in concert with microvessel rarefaction leading to a reduction in H MV, the normal patterns of skeletal muscle oxygenation (Greene et al., 1992; Bos et al., 1995) could be radically altered, contributing to the increased rate of muscle fatigue that has been reported in RRM-hypertensive rats (O’Drobinak and Greene, 1996). Previous studies have determined that erythrocyte velocity within the microcirculation of spontaneously hypertensive rats is higher than that in normotensive animals (Henrich and Hertel, 1979). The present study demonstrates that capillary erythrocyte velocity during resting conditions is also higher in RRM-hypertensive rats (and normotensive rats on high salt diet) than in normotensive rats on low salt diet. However, no differences were evident between groups during maximal dilation of the cremasteric microcirculation with adenosine. The range of values for H MV in the present study corresponds well with previous studies in rat cremaster muscle (House and Lipowsky, 1987) and in the hamster cremaster muscle preparations (Desjardins and Duling, 1987), studies from which the methods employed in the present experiments for determining H MV were taken. The results of this study clearly demonstrate that, under resting conditions, H MV is reduced in the cremaster muscle of rats with acute RRM-hypertension, but not in normotensive rats on high salt diet. However, H MV in the maximally dilated microcirculation was not different between the experimental groups. To our knowledge, the results from the present study represent the first observations addressing the effects of volume-expanded hypertension on skeletal muscle H MV and clearly indicate that this variable is reduced under this condition.
393
Brief Communication
Previous studies suggest a possible mechanism through which H MV is reduced in RRM-hypertensive rats. Mathematical modeling studies have predicted that the microvessel rarefaction that has been demonstrated with acute RRM-hypertension (Hansen-Smith et al., 1996) will increase blood flow heterogeneity within microvascular networks (Greene et al., 1989). This increased flow heterogeneity at microvessel bifurcations will reduce mean microvascular hematocrit as a result of an enhanced manifestation of the network Fahraeus effect (Pries et al., 1986; Cokelet, 1982). In addition, the increased capillary erythrocyte velocity will, by definition, decrease hematocrit within an individual capillary owing to the vessel Fahraeus effect (Pries et al., 1986; Cokelet, 1982). Under conditions of maximal dilation, H MV was not different among the three rat groups. If the discussion in the preceding paragraph regarding the effects of microvessel density on H MV is accurate, these observations suggest that the rapid microvessel rarefaction with RRM-hypertension may be predominantly “functional” in nature, where some microvessels are unperfused under resting conditions. Subsequent addition of potent vasodilator stimuli (e.g., 10 ⫺4 M adenosine) would open microvessels that were “functionally rarefied” in RRM-hypertensive rats, restoring perfusion of the microvascular network to levels comparable to those in normotensive rats. Clearly, the results of these experiments indicate that further investigation of the alterations in microvascular hemodynamics and tissue oxygenation with high salt diet and RRM-hypertension is warranted.
ACKNOWLEDGMENTS The present experiments were supported by NIH Grants HL37374 and HL29587.
REFERENCES Bos, C., Hoofd, L., and Oostendorp, T. (1995). Mathematical model of erythrocytes as point-like sources. Math. Biosci. 125, 165–189. Cokelet, G. R. (1982). Speculation on the cause of low vessel hematocrits in the microcirculation. Microcirculation 2, 1–18. Desjardins, C., and Duling, B. R. (1987). Microvessel hematocrit: Measurement and implications for capillary oxygen transport. Am. J. Physiol. 252, H494 –H503. Fenoy, F. J., and Roman, R. J. (1991). Effect of volume expansion on papillary blood flow and sodium excretion. Am. J. Physiol. 260, F813–F822. Frisbee, J. C., and Lombard, J. H. (1999a). Acute elevations in salt intake and reduced renal mass hypertension compromise arteriolar dilation in rat cremaster muscle. Microvasc. Res. 57, 273–283. Frisbee, J. C., and Lombard, J. H. (1999b). Development and reversibility of altered skeletal muscle arteriolar structure and reactivity with high salt diet and reduced renal mass hypertension. Microcirculation 6, 215–225. Greene, A. S., Tonellato, P. J., Zhang, Z., Lombard, J. H., and Cowley, A. W., Jr. (1992). Effect of microvascular rarefaction on tissue oxygen delivery in hypertension. Am. J. Physiol. 262, H1486 –H1493. Greene, A. S., Tonellato, P. J., Lui, J., Lombard, J. H., and Cowley, A. W., Jr. (1989). Microvascular rarefaction and tissue vascular resistance in hypertension. Am. J. Physiol. 256, H126 –H131. Hansen-Smith, F. M., Morris, L. W., Greene, A. S., and Lombard, J. H. (1996). Rapid microvessel rarefaction with elevated salt intake and reduced renal mass hypertension in rats. Circ. Res. 79, 324 –330. Henrich, H., and Hertel, R. (1979). Hemodynamics and “rarification” of the microvasculature in spontaneously hypertensive rats. Bibl. Anat. 18, 184 –186. House, S. D., and Lipowsky, H. H. (1987). Microvascular hematocrit and red cell flux in rat cremaster muscle. Am. J. Physiol. 252, H211–H222. Lombard, J. H., Hinojosa-Laborde, C., and Cowley, A. W., Jr. (1989). Hemodynamics and microcirculatory alterations in reduced renal mass hypertension. Hypertension 13, 128 –138. O’Drobinak, D. M., and Greene, A. S. (1996). Decreases in steadystate muscle performance and vessel density in reduced renal mass hypertensive rats. Am. J. Physiol. 270, H661–H667. Pries, A. R., Ley, K., and Gaehtgens, P. (1986). Generalization of the Fahraeus principle for microvessel networks. Am. J. Physiol. 251, H1324 –1332.
Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.