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Mechanisms of blood pressure control in conscious rats after chronic treatment with guanethidine
ean systolic and diastolic blood pressure rose significantly in the indomethacin-treated group. However, aspirin nfluence the blood pressure in the second group of patients in comparison to the placebo groups. &art rate y weight remained constant in all groups. Changes of other measured parameters occurred. The mtihypertensive effect of metipranolol in mild to moderate essential hypertension may be related to the system. The changes of blood pressure with metipranolol caused by interaction with aspirin endogenous prostagland and indomethacin are d’ -ent. The reasons for the differences remain to be solved.
Julien, C., Lo, M., Barr&, C. and Sassard, J. Department of PhysioIogy and Clinical Pharmacology, URA CNRS 606, Faculty of Pharmacy, 8 avenue Rockefeller, F-69373, cede-x, France
Early chronic destruction of the peripheral sympathetic nervous system with guanethidine does not lower blood pressure (BP) in normotensive rats but markedly increases its spontaneous variability (Julien et al., 1989). The purpose of this study was to examine the role of the other pressor systems in maintaining the BP level and controlling its variability in conscious rats after sympathectomy. Sympathectomy was achieved by treating male Sprague-Dawley rats with daily S.C. injections of guanethidine between 1 and 13 weeks of age. Control rats received saline. At 14 weeks of age, catheters were inserted via the femoral artery and vein into the lower abdominal aorta and inferior vena cava for recording of BP and intravenous (iv.) injections respectively. After 2 days of recovery, BP was recorded beat by beat in conscious freely moving animals using a computerized technique during 5 consecutive l-hour periods: before and after i.v. injection of either an angiotensin converting enzyme inhibitor (perindopril 2 mg/kg) or a selective vascular antagonist of vasopressin (/3-mercapto-/3, &cyclopentamethylene propionyl’, 0-Me-Tyr *. Args-vasopressin, AVPX 10 pg/kg), after combined administration of both drugs, then after autonomic blockade (chlorisondamine 2.5 mg/kg + phentolamine 5 mg/kg + propranolol5 mg/kg) and finally after hydralazine (3 mg/kg). Evidence for complete functional denervation of the vessels in guanethidine-treated (SX) rats was given by the disappearance of pressor response to tyramine (250 pg/kg iv.) ( - 4 f 2 vs 44 f 1 mmHg). Under basal conditions, the mean BP (MBP) level was slightly lower in SX rats (105 & 3 vs 113 f 2 mmHg, p i 0.05) while its variability, expressed as the standard deviation of the values, was almost doubled (10.7 f 0.9 vs 5.9 4 0.3 mmHg, p =z0.001). After perindopril, i) MBP decreased more markedly (p ( 0.001) in SX than in control rats whether it was administered before(-21+lvs -4+2%>orafter(-28f3vs -7 f 2%) AVPX and ii) the MBP variability was unaffected in control rats while it returned to control levels in SX rats. Alter AVPX, i) MBP decreased only in SX rats when administered after perindopril ( - 13 f 2%) and ii) the MBP variability did not change in either group of rats. After autonomic blockade, i) additional decreases in MBP were observed which were much less marked in SX than in control rats ( - 19 f: 2 vs - 58 f 1% p +z0.001) so that the MBP level became higher (p < 0.001) in SX rats and ii) the hiBP variability decreased in the 2 groups of rats but remained higher (p c 0.01) in SX than in control rats. After hydralazine, i) MBP decreased more in SX than in control rats (- 28 + 3 vs - 19 f 2% p < 0.05) but its final level remained higher in SX rats (41 it 1 vs 36 + 1 mmHg, p < 0.05) and ii) the increased MBP variability in SX rats ret~cned to ncarmal. Conclusion: The renin angiotensin system, and to a lesser extent vasopressin and circulating catecholamines of adrenomedullary origin, contribute to BP maintenance in SX rats. In addition, unidentified non neurohumoral factors also Play a role. The exaggerated BP variability seen in conscious SX rats appears to be largely dependent on the BP level.
JuRen, C.. C. Bsnes. P. Randza and J. Sassard. 1989. Blood pressure lability in the sympathectomized rat, C. R. Acad. Sci.. 308, 219.
Julien, C., Lo, M., Barr&, C. and Sassard, J. Department of PhysioIogy and Clinical Pharmacology, URA CNRS 606, Faculty of Pharmacy, 8 avenue Rockefeller, F-69373, cede-x, France
Early chronic destruction of the peripheral sympathetic nervous system with guanethidine does not lower blood pressure (BP) in normotensive rats but markedly increases its spontaneous variability (Julien et al., 1989). The purpose of this study was to examine the role of the other pressor systems in maintaining the BP level and controlling its variability in conscious rats after sympathectomy. Sympathectomy was achieved by treating male Sprague-Dawley rats with daily S.C. injections of guanethidine between 1 and 13 weeks of age. Control rats received saline. At 14 weeks of age, catheters were inserted via the femoral artery and vein into the lower abdominal aorta and inferior vena cava for recording of BP and intravenous (iv.) injections respectively. After 2 days of recovery, BP was recorded beat by beat in conscious freely moving animals using a computerized technique during 5 consecutive l-hour periods: before and after i.v. injection of either an angiotensin converting enzyme inhibitor (perindopril 2 mg/kg) or a selective vascular antagonist of vasopressin (/3-mercapto-/3, &cyclopentamethylene propionyl’, 0-Me-Tyr *. Args-vasopressin, AVPX 10 pg/kg), after combined administration of both drugs, then after autonomic blockade (chlorisondamine 2.5 mg/kg + phentolamine 5 mg/kg + propranolol5 mg/kg) and finally after hydralazine (3 mg/kg). Evidence for complete functional denervation of the vessels in guanethidine-treated (SX) rats was given by the disappearance of pressor response to tyramine (250 pg/kg iv.) ( - 4 f 2 vs 44 f 1 mmHg). Under basal conditions, the mean BP (MBP) level was slightly lower in SX rats (105 & 3 vs 113 f 2 mmHg, p i 0.05) while its variability, expressed as the standard deviation of the values, was almost doubled (10.7 f 0.9 vs 5.9 4 0.3 mmHg, p =z0.001). After perindopril, i) MBP decreased more markedly (p ( 0.001) in SX than in control rats whether it was administered before(-21+lvs -4+2%>orafter(-28f3vs -7 f 2%) AVPX and ii) the MBP variability was unaffected in control rats while it returned to control levels in SX rats. Alter AVPX, i) MBP decreased only in SX rats when administered after perindopril ( - 13 f 2%) and ii) the MBP variability did not change in either group of rats. After autonomic blockade, i) additional decreases in MBP were observed which were much less marked in SX than in control rats ( - 19 f: 2 vs - 58 f 1% p +z0.001) so that the MBP level became higher (p < 0.001) in SX rats and ii) the hiBP variability decreased in the 2 groups of rats but remained higher (p c 0.01) in SX than in control rats. After hydralazine, i) MBP decreased more in SX than in control rats (- 28 + 3 vs - 19 f 2% p < 0.05) but its final level remained higher in SX rats (41 it 1 vs 36 + 1 mmHg, p < 0.05) and ii) the increased MBP variability in SX rats ret~cned to ncarmal. Conclusion: The renin angiotensin system, and to a lesser extent vasopressin and circulating catecholamines of adrenomedullary origin, contribute to BP maintenance in SX rats. In addition, unidentified non neurohumoral factors also Play a role. The exaggerated BP variability seen in conscious SX rats appears to be largely dependent on the BP level.
JuRen, C.. C. Bsnes. P. Randza and J. Sassard. 1989. Blood pressure lability in the sympathectomized rat, C. R. Acad. Sci.. 308, 219.