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Silent Aortic Regurgitation in Hypertension
Conclusion: A hypertension quality improvement program based on active audit and feedback at multiple primary care sites which include ethnic minorities and complicated patients is feasible. Individual risk factors are controlled to or near goal in many. The most striking ethnic difference is in LDL– c control which appears to reflect the lower use of statin drugs in African Americans (Figure 2). Such findings suggest that the database can be used to guide education and interventions to improve treatment and reduce disparities. POSTMENOPAUSAL HYPERTENSION IS LINKED TO DECREASED RENAL ENOS ACTIVITY, INCREASED RENAL AT1 RECEPTOR EXPRESSION AND SALTSENSITIVITY I. H. Schulman1,2, L. M Harrison-Bernard3, L. Raij1,2. 1 Nephrology-Hypertension Division, VA Medical Center and 2 Vascular Biology Institute, University of Miami, Miami, FL and 3Department of Physiology, Tulane University Health Sciences Center, New Orleans, LA. In hypertension, salt-sensitivity is a marker for a disproportionate susceptibility to cardiovascular and renal disease. After menopause, the incidence of both salt sensitivity and hypertension increases in women. The functional balance between angiotensin II (Ang II) and nitric oxide (NO) plays a key role in modulating salt- sensitivity. Estrogen has been shown to downregulate angiotensin type 1 (AT1) receptor expression and to increase the bioavailability of endothelium-derived NO, which decreases AT1 receptor expression. The present study tests the hypothesis that in the presence of genetic salt-sensitivity, deficiency of estrogens after ovariectomy (OVX) is linked to a decrease in renal NO bioavailability and a concomitant functional upregulation of Ang II action that lowers the threshold for the hypertensinogenic effect of salt. Female Dahl salt resistant (DR), Dahl salt sensitive (DS), Wistar Kyoto (WKY), and spontaneously hypertensive (SHR) rats underwent bilateral OVX or sham surgery (SHX) and were fed a normal salt diet (0.5% NaCl) for 14 weeks. Systolic blood pressures (SBP) were measured every 2 weeks and the left ventricular (LV) weight and endothelial NO synthase activity (eNOS) were measured at the end of the study period. SBP, LV weight, and eNOS activity were not significantly different between OVX and SHX for DR, WKY and SHR groups. However, at the end of 14 weeks of normal salt diet, DS OVX but not SHX rats developed hypertension (160 ⫹/- 3 vs. 136 ⫹/- 3 mmHg; p⬍0.05) accompanied by a significant increase in LV weight (0.638 ⫹/- 0.27 vs. 0.560 ⫹/- 0.019 g; p⬍0.05) and reduction in renal medullary eNOS activity (13 ⫹/- 1 vs. 9 ⫹/- 1; p⬍0.05). Development of hypertension in DS OVX rats was prevented by estrogen replacement (132 ⫹/- 3 mmHg), AT1 receptor blockade (119 ⫹/- 3 mmHg), or feeding a low salt diet (0.1% NaCl; 129 ⫹/- 4 mmHg). Moreover, renal AT1 receptor protein expression was significantly elevated 2-fold in DS OVX relative to SHX rats, an effect that was prevented by estrogen replacement. Clinically we infer that after menopause, in women genetically prone to salt-sensitivity, estrogen deficiency promotes a decline in renal eNOS activity and overexpression of renal AT1 receptors that fosters the development of hypertension. DISTAL TUBULE RENIN EXPRESSION IN ANGIOTENSIN (ANG) II-INFUSED RATS M. Prieto-Carrasquero1, L. M Harrison-Bernard1, K. S. HeringSmith2, H. Kobori1, L. L. Hamm2, L. G. Navar1. Hypertension and Renal Center of Excellence, Departments of 1Physiology and 2 Medicine - Division of Nephrology, Tulane University Health Sciences Center, New Orleans, LA. AngII-induced hypertension is associated with increased intrarenal angiotensinogen (AGT) formation with increased proximal tubule secretion and urinary AGT excretion. The identification of renin in distal tubule nephron segments provides a possible pathway for AngI generation from proximally delivered AGT. To examine the chronic effects of AngII infusions on distal tubular renin, we evaluated renin protein and mRNA expressions in
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AngII-infused hypertensive rats. Kidneys from sham operated (n⫽8) and chronically AngII-infused (80 ng/kg/min, 13 days, n⫽8) rats were processed for immunohistochemistry, Western blot and RT-PCR techniques. AngII infusion significantly increased systolic blood pressure (181⫾4 vs 115⫾5mmHg; day 11) despite a marked suppression of plasma renin activity (1.5⫾0.5 vs 8.3⫾0.9 ngAngI䡠mL䡠h⫺1) compared to sham. Renin immunohistochemistry studies showed suppression in juxtaglomerular cells in AngIIinfused rats compared to sham (0.14⫾0.05 vs 1.0⫾0.11 units; P⬍0.001). Renin and aquaporin 2 were colocalized in principal cells of connecting tubules, cortical and medullary collecting ducts. Spatial density of collecting duct segment renin immunoreactivity was higher in AngII-infused than sham rats (1.0⫾0.1 vs 6.40⫾1.4 cortex; 1.0⫾0.2 vs 2.5⫾0.3 units medulla; P⬍0.001). Western blot analysis of kidney medulla protein showed that AngII-infused rats had 1.9⫾0.1-fold increased renin compared to controls (P⬍0.05). RT-PCR specific primers for the Renin-1c gene demonstrated the expected 560-bp product in all analyzed kidney medulla samples. No product was observed in absence of RT enzyme. DNA sequencing of the products from cortex and medulla reported 99% identity to pre-prorenin/prorenin. Similar approaches using a transformed cortical collecting duct cell line (M-1 cells) confirmed the presence of renin mRNA indicating that renin is synthesized in collecting duct cells. The results demonstrate that AngII infusion stimulates renin protein expression in cortical and medullary collecting ducts. Detection of renin transcript in renal medulla, which is devoid of JG apparatus indicates that renin is synthesized in this region and not simply due to uptake of renin from the interstitium. The enhancement of distal tubular renin provides a mechanism by which AngI can be generated from proximally delivered AGT thus contributing to distal intratubular AngII levels in AngII-dependent hypertension. Support from NIH and Louisiana Board and Regents. SILENT AORTIC REGURGITATION IN HYPERTENSION M. Motallebi, R. Dickerson, R. Douglas, K. Ravakhah. Department of Medicine, Huron Hospital, East Cleveland, OH. Introduction: Aortic Regurgitation (AR) is a common finding in echocardiograms. Although some early reports suggested hypertension (HTN) as a predisposing factor to aortic root enlargement and AR, such an association has not been shown in recent pathological and echocardiographic studies. In fact, the incidence and the clinical importance of silent or sub-clinical AR in hypertensive populations is unknown. The present case-control study was undertaken to explore the relations of HTN with trivial (1⫹) to mild (2⫹) AR. Subjects & Methods: One thousand echocardiograms with Doppler records of 1000 inpatients 50 years or older were reviewed for presence of 1⫹ or 2⫹ AR. Patients with a history of aortic valve operation/prosthesis, history of rheumatic heart disease or rheumatic fever, or documented aortic valve disease were excluded. Twenty-two patients had moderate (3⫹) to severe (4⫹) AR and were excluded as well. A total of 140 patients found to have 1⫹ to 2⫹ AR became our study group (AR⫹). A control group of 140 individuals was selected randomly from the population with no AR (AR-). Patients in both study and control groups were screened for the presence of a history of HTN, duration of anti-hypertensive therapy and the systolic and diastolic blood pressure at the time of hospital admission. HTN⫹ was defined as a history of HTN and on medical treatment. HTN- was defined as lack of the history or medical treatment. Admission HTN was diagnosed based on a blood pressure of 140/90 mmHg or more. Patients were divided into four sub-groups, as follows: AR⫹ and HTN⫹ (94 patients), AR⫹ and HTN- (46 patients), AR- and HTN⫹ (78 patients), and AR- and HTN- (62 patients). Other variables such as sex, age, mean arterial pressure, pulse pressure and aortic root dimension were defined and documented for all patients in both groups as well. Statistical testing was applied to discover the association of occurrence of AR with duration of anti-hypertensive therapy (as an indicator of duration
May 2004 Volume 327 Number 5
of HTN) as well as other variables such as sex, age, admission systolic & diastolic pressures, aortic root dimension, mean arterial pressure, and pulse pressure. Results: The multivariate logistic regression analysis identified the presence of HTN as being significantly associated with increased odds for the occurrence of AR. Analysis also demonstrated an association between increased aortic root dimension and AR. Furthermore, these odds were increased for each additional year of duration of treatment and each additional cm measurement of aortic root dimension in the definitive multivariate model. Conclusion: The result of our study suggests that the presence of HTN increases the odds of silent aortic regurgitation. Aortic root widening showed a similar correlation. The clinical implication and consequences of this silent aortic regurgitation in hypertensive populations is unknown. Further, it is uncertain whether successful treatment could decrease or slow down the occurrence of AR. Interestingly, chronicity rather than severity of hypertension is found to be a predictor in the occurrence of AR. EFFECT OF CARDIOVASCULAR THERAPY ON ARTERIAL COMPLIANCE A. Rastogi, D. Lackland. Department of Biometry & Epidemiology, Medical University of South Carolina, Charleston, SC. Decreased arterial elasticity is known to be an early indicator of the atherosclerotic process. The effect of common cardiovascular therapies is unknown on this early indicator. This study examines the effect of anticoagulant, diuretic, beta-blocker, angiotensin converting enzyme (ACE) inhibitor, calcium channel blocker, statin, and vitamin E therapy on a convenience sample of 141 subjects. Subjects were recruited from patients presenting for care at the Medical University of South Carolina College of Dental Medicine. Enrolled subjects completed an interviewer assisted health survey. The survey collected information on health history and demographic information. The subjects’ small artery compliance (C2) was determined by non-invasive measurement of their arterial pulse-wave using the CR-2000 Cardiovascular Profiler (HDI). C2 was categorized according to age and sex as normal, borderline, or abnormal. The effects of anticoagulant, diuretic, beta-blocker, ACE inhibitor, calcium channel blocker, statin, and vitamin E therapy was quantified using ordinal logistic regression. Of the 141 subjects, 64 were not on any of the therapies examined, 55 were taking anticoagulants , 20 were taking diuretics, 11 were taking beta-blockers, 16 were taking ACE inhibitors, 12 were taking calcium channel blockers, 32 were taking statins, and 21 were taking Vitamin E supplements. Logistic regression found none of these therapies to have a significant effect on C2 category. The odds ratio and 95% confidence interval for each therapy was: anticoagulant 1.31 (0.56–2.91), diuretic 1.41 (0.42– 4.7), beta-blocker 0.41 (0.1–1.63), ACE inhibitor 1.18 (0.33–4.16), calcium channel blocker 0.89 (0.22–3.7), statin 1.4 (0.54 –3.67), and vitamin E 0.56 (0.21–1.54). This study was unable to find a statistically significant effect of common cardiovascular therapies on small artery elasticity. IMBALANCE OF ENDOGENOUS BRAIN ANGIOTENSIN II AND ANGIOTENSIN-(1–7) CONTRIBUTES TO DIMINISHED BARORECEPTOR REFLEX FUNCTION IN AGING RATS A. Sakima, E. Tommasi, D. Averill, C.M. Ferrario, D.I. Diz. Hypertension & Vascular Disease Center Wake Forest University Health Science Center, Winston Salem, NC Endogenous brain angiotensin (Ang) 11 attenuates and Ang-(1–7) facilitates baroreceptor reflex in young adult rats. We determined the role of the two Ang peptides in the age-related impairment in baroreceptor reflex function that occurs in association with increased blood pressure. Under urethane/chloralose anesthesia, baroreceptor reflex control of heart rate and reflex cardiac vagal chemosensitive fiber activation (CVA) were tested in young (12 16 wks) and older (70 - 78 wks) Sprague-Dawley rats before and after bilateral nucleus tractus solitarii (NTS) injection of an AT1 receptor antagonist, candesartan (CAN; 24 pmol/120 nl ) followed
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
by an angiotensin-(1–7) antagonist, (D-Ala7)-angiotensin-(1–7) (D-Ala; 144 fmol/120 nl). The slope of the relationship between changes in blood pressure and heart rate in response to graded doses of phenylephrine was used to determine baroreflex sensitivity, which was significantly greater than in older rats. Reflex control of heart rate was facilitated ⬃45% following bilateral injection of CAN into the NTS in young rats (1.1 ⫹ 0.2 baseline vs 1.6 ⫾ 0.2 msec/mm Hg post-CAN; P ⬍ 0.05). Injection of D-Ala into the NTS reversed the facilitation induced by AT1 blockade. In contrast, the baroreflex slope was attenuated ⬃32% following an initial injection of D-Ala in young rats and this was reversed by subsequent CAN injection into the NTS. In older rats, facilitation with CAN tended to be less with no reversal by D-Ala. CAN and D-Ala had no effect on reflex responses to CVA by phenylbiguanide at either age. Thus, endogenous brain Ang 11 and Ang(1–7) have opposing actions to influence resting baroreceptor reflex function. An imbalance and/or attenuation of Ang-(1–7) effects in NTS of older rats may contribute to diminished baroreflex function. Support: HL-51952 APPLICATION OF MEASURED HYPERCAPNICHYPOXIC PATIENTS BREATHING PROTOCOLS IN REHABILITATION OF ASTHMATIC-HYPERTENSIVE FEMALE PATIENTS R.L. Sydorchuk 1, L.P. Sydorchuk2, I. I. Sydorchuk3. 1General Surgery, 2Family Medicine, 2Clinical Immunology and Allergology Departments of the Bucovinian State Medical Academy, Chernivtsi, Ukraine Background: Although combination of asthma and arterial hypertension in Caucasian females is not a rare condition its significance is under-evaluated. The aim of the study was to evaluate the special measured hypercapnic-hypoxic breathing protocols effects on respiratory system functional state in asthmatic female patients with essential hypertension. Method: Research protocol included observation of 70 female patients with mild asthma combined with mild essential hypertension, from 32 to 52 years old (mean 42.15⫾3.87) who formed the 1st (research) group. Control group (2nd) included individuals, who were not suffering from any chronic respiratory disease in anamnesis, but have mild essential hypertension. Hypercapnic-hypoxic breathing protocols were based on measured breathing exercises with different length of breathing phases: inhalation, exhalation, holding patients’ breath with retention of the breath on expiration phase (3–4 seconds). Breathing exercises were administered under control of oxygen and carbooxygen partial blood pressure, exhaled air gases chronometric analysis, individual patient’s perceptibility to the hypercapnia and hypoxia levels during 6 – 8 weeks, for 20 min 3 times per day using special facility. Parameters of the respiratory system function were examined by the method of computer spirography (Jaeger®, Germany) before and after the course of measured breathing exercises administration. Results: Before hypercapnic-hypoxic breathing protocol administration such predictive and active parameters of computer spirography as Maximum Voluntary Ventilation (MVV), Forced Vital Capacity (FVC), Forced Expiratory Volume after 1 s (FEV 1). FEV 1 as % of lnspiratory Vital Capacity (FEV 1%VCIN), FEV 1 as % of FVC (FEV 1 E), and Peak lnspiratory and Expiratory Flow (PIF, PEF) were evaluated and it was found that they were significantly lower in 98% of the 1st group patients (p⬍0.05). After hypercapnic-hypoxic breathing protocol administration, data of all active parameters mentioned above in 78% patients of the 1st group significantly improved (p⬍0.05); in 5% patients of this group such active parameters as MVV, FEV 1%VCIN, FEV 1 E increased uncertainly (p0.05); in 17% patients of research group such active parameters as FVC, FEV 1, PEF, PIF increased significantly (p⬍0.05) but data of FEV 1%VCIN and FEV 1E increased uncertainly (p0.05). Conclusion: Thus, administration of the measured hypercapnichypoxic breathing protocols in hypertensive-asthmatic female patients’ rehabilitation is a cost-effective method for significant improvement of the respiratory functional state active parameters.
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AngII-infused hypertensive rats. Kidneys from sham operated (n⫽8) and chronically AngII-infused (80 ng/kg/min, 13 days, n⫽8) rats were processed for immunohistochemistry, Western blot and RT-PCR techniques. AngII infusion significantly increased systolic blood pressure (181⫾4 vs 115⫾5mmHg; day 11) despite a marked suppression of plasma renin activity (1.5⫾0.5 vs 8.3⫾0.9 ngAngI䡠mL䡠h⫺1) compared to sham. Renin immunohistochemistry studies showed suppression in juxtaglomerular cells in AngIIinfused rats compared to sham (0.14⫾0.05 vs 1.0⫾0.11 units; P⬍0.001). Renin and aquaporin 2 were colocalized in principal cells of connecting tubules, cortical and medullary collecting ducts. Spatial density of collecting duct segment renin immunoreactivity was higher in AngII-infused than sham rats (1.0⫾0.1 vs 6.40⫾1.4 cortex; 1.0⫾0.2 vs 2.5⫾0.3 units medulla; P⬍0.001). Western blot analysis of kidney medulla protein showed that AngII-infused rats had 1.9⫾0.1-fold increased renin compared to controls (P⬍0.05). RT-PCR specific primers for the Renin-1c gene demonstrated the expected 560-bp product in all analyzed kidney medulla samples. No product was observed in absence of RT enzyme. DNA sequencing of the products from cortex and medulla reported 99% identity to pre-prorenin/prorenin. Similar approaches using a transformed cortical collecting duct cell line (M-1 cells) confirmed the presence of renin mRNA indicating that renin is synthesized in collecting duct cells. The results demonstrate that AngII infusion stimulates renin protein expression in cortical and medullary collecting ducts. Detection of renin transcript in renal medulla, which is devoid of JG apparatus indicates that renin is synthesized in this region and not simply due to uptake of renin from the interstitium. The enhancement of distal tubular renin provides a mechanism by which AngI can be generated from proximally delivered AGT thus contributing to distal intratubular AngII levels in AngII-dependent hypertension. Support from NIH and Louisiana Board and Regents. SILENT AORTIC REGURGITATION IN HYPERTENSION M. Motallebi, R. Dickerson, R. Douglas, K. Ravakhah. Department of Medicine, Huron Hospital, East Cleveland, OH. Introduction: Aortic Regurgitation (AR) is a common finding in echocardiograms. Although some early reports suggested hypertension (HTN) as a predisposing factor to aortic root enlargement and AR, such an association has not been shown in recent pathological and echocardiographic studies. In fact, the incidence and the clinical importance of silent or sub-clinical AR in hypertensive populations is unknown. The present case-control study was undertaken to explore the relations of HTN with trivial (1⫹) to mild (2⫹) AR. Subjects & Methods: One thousand echocardiograms with Doppler records of 1000 inpatients 50 years or older were reviewed for presence of 1⫹ or 2⫹ AR. Patients with a history of aortic valve operation/prosthesis, history of rheumatic heart disease or rheumatic fever, or documented aortic valve disease were excluded. Twenty-two patients had moderate (3⫹) to severe (4⫹) AR and were excluded as well. A total of 140 patients found to have 1⫹ to 2⫹ AR became our study group (AR⫹). A control group of 140 individuals was selected randomly from the population with no AR (AR-). Patients in both study and control groups were screened for the presence of a history of HTN, duration of anti-hypertensive therapy and the systolic and diastolic blood pressure at the time of hospital admission. HTN⫹ was defined as a history of HTN and on medical treatment. HTN- was defined as lack of the history or medical treatment. Admission HTN was diagnosed based on a blood pressure of 140/90 mmHg or more. Patients were divided into four sub-groups, as follows: AR⫹ and HTN⫹ (94 patients), AR⫹ and HTN- (46 patients), AR- and HTN⫹ (78 patients), and AR- and HTN- (62 patients). Other variables such as sex, age, mean arterial pressure, pulse pressure and aortic root dimension were defined and documented for all patients in both groups as well. Statistical testing was applied to discover the association of occurrence of AR with duration of anti-hypertensive therapy (as an indicator of duration
May 2004 Volume 327 Number 5
of HTN) as well as other variables such as sex, age, admission systolic & diastolic pressures, aortic root dimension, mean arterial pressure, and pulse pressure. Results: The multivariate logistic regression analysis identified the presence of HTN as being significantly associated with increased odds for the occurrence of AR. Analysis also demonstrated an association between increased aortic root dimension and AR. Furthermore, these odds were increased for each additional year of duration of treatment and each additional cm measurement of aortic root dimension in the definitive multivariate model. Conclusion: The result of our study suggests that the presence of HTN increases the odds of silent aortic regurgitation. Aortic root widening showed a similar correlation. The clinical implication and consequences of this silent aortic regurgitation in hypertensive populations is unknown. Further, it is uncertain whether successful treatment could decrease or slow down the occurrence of AR. Interestingly, chronicity rather than severity of hypertension is found to be a predictor in the occurrence of AR. EFFECT OF CARDIOVASCULAR THERAPY ON ARTERIAL COMPLIANCE A. Rastogi, D. Lackland. Department of Biometry & Epidemiology, Medical University of South Carolina, Charleston, SC. Decreased arterial elasticity is known to be an early indicator of the atherosclerotic process. The effect of common cardiovascular therapies is unknown on this early indicator. This study examines the effect of anticoagulant, diuretic, beta-blocker, angiotensin converting enzyme (ACE) inhibitor, calcium channel blocker, statin, and vitamin E therapy on a convenience sample of 141 subjects. Subjects were recruited from patients presenting for care at the Medical University of South Carolina College of Dental Medicine. Enrolled subjects completed an interviewer assisted health survey. The survey collected information on health history and demographic information. The subjects’ small artery compliance (C2) was determined by non-invasive measurement of their arterial pulse-wave using the CR-2000 Cardiovascular Profiler (HDI). C2 was categorized according to age and sex as normal, borderline, or abnormal. The effects of anticoagulant, diuretic, beta-blocker, ACE inhibitor, calcium channel blocker, statin, and vitamin E therapy was quantified using ordinal logistic regression. Of the 141 subjects, 64 were not on any of the therapies examined, 55 were taking anticoagulants , 20 were taking diuretics, 11 were taking beta-blockers, 16 were taking ACE inhibitors, 12 were taking calcium channel blockers, 32 were taking statins, and 21 were taking Vitamin E supplements. Logistic regression found none of these therapies to have a significant effect on C2 category. The odds ratio and 95% confidence interval for each therapy was: anticoagulant 1.31 (0.56–2.91), diuretic 1.41 (0.42– 4.7), beta-blocker 0.41 (0.1–1.63), ACE inhibitor 1.18 (0.33–4.16), calcium channel blocker 0.89 (0.22–3.7), statin 1.4 (0.54 –3.67), and vitamin E 0.56 (0.21–1.54). This study was unable to find a statistically significant effect of common cardiovascular therapies on small artery elasticity. IMBALANCE OF ENDOGENOUS BRAIN ANGIOTENSIN II AND ANGIOTENSIN-(1–7) CONTRIBUTES TO DIMINISHED BARORECEPTOR REFLEX FUNCTION IN AGING RATS A. Sakima, E. Tommasi, D. Averill, C.M. Ferrario, D.I. Diz. Hypertension & Vascular Disease Center Wake Forest University Health Science Center, Winston Salem, NC Endogenous brain angiotensin (Ang) 11 attenuates and Ang-(1–7) facilitates baroreceptor reflex in young adult rats. We determined the role of the two Ang peptides in the age-related impairment in baroreceptor reflex function that occurs in association with increased blood pressure. Under urethane/chloralose anesthesia, baroreceptor reflex control of heart rate and reflex cardiac vagal chemosensitive fiber activation (CVA) were tested in young (12 16 wks) and older (70 - 78 wks) Sprague-Dawley rats before and after bilateral nucleus tractus solitarii (NTS) injection of an AT1 receptor antagonist, candesartan (CAN; 24 pmol/120 nl ) followed
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
by an angiotensin-(1–7) antagonist, (D-Ala7)-angiotensin-(1–7) (D-Ala; 144 fmol/120 nl). The slope of the relationship between changes in blood pressure and heart rate in response to graded doses of phenylephrine was used to determine baroreflex sensitivity, which was significantly greater than in older rats. Reflex control of heart rate was facilitated ⬃45% following bilateral injection of CAN into the NTS in young rats (1.1 ⫹ 0.2 baseline vs 1.6 ⫾ 0.2 msec/mm Hg post-CAN; P ⬍ 0.05). Injection of D-Ala into the NTS reversed the facilitation induced by AT1 blockade. In contrast, the baroreflex slope was attenuated ⬃32% following an initial injection of D-Ala in young rats and this was reversed by subsequent CAN injection into the NTS. In older rats, facilitation with CAN tended to be less with no reversal by D-Ala. CAN and D-Ala had no effect on reflex responses to CVA by phenylbiguanide at either age. Thus, endogenous brain Ang 11 and Ang(1–7) have opposing actions to influence resting baroreceptor reflex function. An imbalance and/or attenuation of Ang-(1–7) effects in NTS of older rats may contribute to diminished baroreflex function. Support: HL-51952 APPLICATION OF MEASURED HYPERCAPNICHYPOXIC PATIENTS BREATHING PROTOCOLS IN REHABILITATION OF ASTHMATIC-HYPERTENSIVE FEMALE PATIENTS R.L. Sydorchuk 1, L.P. Sydorchuk2, I. I. Sydorchuk3. 1General Surgery, 2Family Medicine, 2Clinical Immunology and Allergology Departments of the Bucovinian State Medical Academy, Chernivtsi, Ukraine Background: Although combination of asthma and arterial hypertension in Caucasian females is not a rare condition its significance is under-evaluated. The aim of the study was to evaluate the special measured hypercapnic-hypoxic breathing protocols effects on respiratory system functional state in asthmatic female patients with essential hypertension. Method: Research protocol included observation of 70 female patients with mild asthma combined with mild essential hypertension, from 32 to 52 years old (mean 42.15⫾3.87) who formed the 1st (research) group. Control group (2nd) included individuals, who were not suffering from any chronic respiratory disease in anamnesis, but have mild essential hypertension. Hypercapnic-hypoxic breathing protocols were based on measured breathing exercises with different length of breathing phases: inhalation, exhalation, holding patients’ breath with retention of the breath on expiration phase (3–4 seconds). Breathing exercises were administered under control of oxygen and carbooxygen partial blood pressure, exhaled air gases chronometric analysis, individual patient’s perceptibility to the hypercapnia and hypoxia levels during 6 – 8 weeks, for 20 min 3 times per day using special facility. Parameters of the respiratory system function were examined by the method of computer spirography (Jaeger®, Germany) before and after the course of measured breathing exercises administration. Results: Before hypercapnic-hypoxic breathing protocol administration such predictive and active parameters of computer spirography as Maximum Voluntary Ventilation (MVV), Forced Vital Capacity (FVC), Forced Expiratory Volume after 1 s (FEV 1). FEV 1 as % of lnspiratory Vital Capacity (FEV 1%VCIN), FEV 1 as % of FVC (FEV 1 E), and Peak lnspiratory and Expiratory Flow (PIF, PEF) were evaluated and it was found that they were significantly lower in 98% of the 1st group patients (p⬍0.05). After hypercapnic-hypoxic breathing protocol administration, data of all active parameters mentioned above in 78% patients of the 1st group significantly improved (p⬍0.05); in 5% patients of this group such active parameters as MVV, FEV 1%VCIN, FEV 1 E increased uncertainly (p0.05); in 17% patients of research group such active parameters as FVC, FEV 1, PEF, PIF increased significantly (p⬍0.05) but data of FEV 1%VCIN and FEV 1E increased uncertainly (p0.05). Conclusion: Thus, administration of the measured hypercapnichypoxic breathing protocols in hypertensive-asthmatic female patients’ rehabilitation is a cost-effective method for significant improvement of the respiratory functional state active parameters.
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