Oral rapamycin attenuates atherosclerosis without affecting the arterial responsiveness of resistance vessels in apolipoprotein E-deficient mice

The objective of the present study was to assess the effects of the immunosuppressant rapamycin (Rapamune®, Sirolimus) on both resistance vessel responsiveness and atherosclerosis in apolipoprotein E-deficient 8-week-old male mice fed a normal rodent diet. Norepinephrine (NE)-induced vasoconstriction, acetylcholine (ACh)- and sodium nitroprusside (SNP)-induced vasorelaxation of isolated mesenteric bed, and atherosclerotic lesions were evaluated. After 12 weeks of orally administered rapamycin (5 mg·kg-1·day-1, N = 9) and compared with untreated (control, N = 9) animals, rapamycin treatment did not modify either NE-induced vasoconstriction (maximal response: 114 ± 4 vs 124 ± 10 mmHg, respectively) or ACh- (maximal response: 51 ± 8 vs 53 ± 5 percent, respectively) and SNP-induced vasorelaxation (maximal response: 73 ± 6 vs 74 ± 6 percent, respectively) of the isolated vascular mesenteric bed. Despite increased total cholesterol in treated mice (982 ± 59 vs 722 ± 49 mg/dL, P < 0.01), lipid deposition on the aorta wall vessel was significantly less in rapamycin-treated animals (37 ± 12 vs 68 ± 8 µm² x 10³). These results indicate that orally administered rapamycin is effective in attenuating the progression of atherosclerotic plaque without affecting the responsiveness of resistance vessels, supporting the idea that this immunosuppressant agent might be of potential benefit against atherosclerosis in patients undergoing therapy.

Endogenous angiotensin II modulates nNOS expression in renovascular hypertension

Nitric oxide (NO) influences renal blood flow mainly as a result of neuronal nitric oxide synthase (nNOS). Nevertheless, it is unclear how nNOS expression is modulated by endogenous angiotensin II, an inhibitor of NO function. We tested the hypothesis that the angiotensin II AT1 receptor and oxidative stress mediated by NADPH oxidase contribute to the modulation of renal nNOS expression in two-kidney, one-clip (2K1C) hypertensive rats. Experiments were performed on male Wistar rats (150 to 170 g body weight) divided into 2K1C (N = 19) and sham-operated (N = 19) groups. nNOS expression in kidneys of 2K1C hypertensive rats (N = 9) was compared by Western blotting to that of 2K1C rats treated with low doses of the AT1 antagonist losartan (10 mg·kg-1·day-1; N = 5) or the superoxide scavenger tempol (0.2 mmol·kg-1·day-1; N = 5), which still remain hypertensive. After 28 days, nNOS expression was significantly increased by 1.7-fold in the clipped kidneys of 2K1C rats and by 3-fold in the non-clipped kidneys of 2K1C rats compared with sham rats, but was normalized by losartan. With tempol treatment, nNOS expression increased 2-fold in the clipped kidneys and 1.4-fold in the non-clipped kidneys compared with sham rats. The changes in nNOS expression were not followed by changes in the enzyme activity, as measured indirectly by the cGMP method. In conclusion, AT1 receptors and oxidative stress seem to be primary stimuli for increased nNOS expression, but this up-regulation does not result in higher enzyme activity.

Influence of renal denervation on blood pressure, sodium and water excretion in acute total obstructive apnea in rats

Obstructive apnea (OA) can exert significant effects on renal sympathetic nerve activity (RSNA) and hemodynamic parameters. The present study focuses on the modulatory actions of RSNA on OA-induced sodium and water retention. The experiments were performed in renal-denervated rats (D; N = 9), which were compared to sham (S; N = 9) rats. Mean arterial pressure (MAP) and heart rate (HR) were assessed via an intrafemoral catheter. A catheter was inserted into the bladder for urinary measurements. OA episodes were induced via occlusion of the catheter inserted into the trachea. After an equilibration period, OA was induced for 20 s every 2 min and the changes in urine, MAP, HR and RSNA were recorded. Renal denervation did not alter resting MAP (S: 113 ± 4 vs D: 115 ± 4 mmHg) or HR (S: 340 ± 12 vs D: 368 ± 11 bpm). An OA episode resulted in decreased HR and MAP in both groups, but D rats showed exacerbated hypotension and attenuated bradycardia (S: -12 ± 1 mmHg and -16 ± 2 bpm vs D: -16 ± 1 mmHg and 9 ± 2 bpm; P < 0.01). The basal urinary parameters did not change during or after OA in S rats. However, D rats showed significant increases both during and after OA. Renal sympathetic nerve activity in S rats increased (34 ± 9 percent) during apnea episodes. These results indicate that renal denervation induces elevations of sodium content and urine volume and alters bradycardia and hypotension patterns during total OA in unconscious rats.

Transitory increased blood pressure after upper airway surgery for snoring and sleep apnea correlates with the apnea-hypopnea respiratory disturbance index

A transitory increase in blood pressure (BP) is observed following upper airway surgery for obstructive sleep apnea syndrome but the mechanisms implicated are not yet well understood. The objective of the present study was to evaluate changes in BP and heart rate (HR) and putative factors after uvulopalatopharyngoplasty and septoplasty in normotensive snorers. Patients (N = 10) were instrumented for 24-h ambulatory BP monitoring, nocturnal respiratory monitoring and urinary catecholamine level evaluation one day before surgery and on the day of surgery. The influence of postsurgery pain was prevented by analgesic therapy as confirmed using a visual analog scale of pain. Compared with preoperative values, there was a significant (P < 0.05) increase in nighttime but not daytime systolic BP (119 ± 5 vs 107 ± 3 mmHg), diastolic BP (72 ± 4 vs 67 ± 2 mmHg), HR (67 ± 4 vs 57 ± 2 bpm), respiratory disturbance index (RDI) characterized by apnea-hypopnea (30 ± 10 vs 13 ± 4 events/h of sleep) and norepinephrine levels (22.0 ± 4.7 vs 11.0 ± 1.3 æg l-1 12 h-1) after surgery. A positive correlation was found between individual variations of BP and individual variations of RDI (r = 0.81, P < 0.01) but not between BP or RDI and catecholamines. The visual analog scale of pain showed similar stress levels on the day before and after surgery (6.0 ± 0.8 vs 5.0 ± 0.9 cm, respectively). These data strongly suggest that the cardiovascular changes observed in patients who underwent uvulopalatopharyngoplasty and septoplasty were due to the increased postoperative RDI.

Ambulatory blood pressure and Doppler echocardiographic indexes of borderline hypertensive men presenting an exaggerated blood pressure response during dynamic exercise

Borderline hypertension (BH) has been associated with an exaggerated blood pressure (BP) response during laboratory stressors. However, the incidence of target organ damage in this condition and its relation to BP hyperreactivity is an unsettled issue. Thus, we assessed the Doppler echocardiographic profile of a group of BH men (N = 36) according to office BP measurements with exaggerated BP in the cycloergometric test. A group of normotensive men (NT, N = 36) with a normal BP response during the cycloergometric test was used as control. To assess vascular function and reactivity, all subjects were submitted to the cold pressor test. Before Doppler echocardiography, the BP profile of all subjects was evaluated by 24-h ambulatory BP monitoring. All subjects from the NT group presented normal monitored levels of BP. In contrast, 19 subjects from the original BH group presented normal monitored BP levels and 17 presented elevated monitored BP levels. In the NT group all Doppler echocardiographic indexes were normal. All subjects from the original BH group presented normal left ventricular mass and geometrical pattern. However, in the subjects with elevated monitored BP levels, fractional shortening was greater, isovolumetric relaxation time longer, and early to late flow velocity ratio was reduced in relation to subjects from the original BH group with normal monitored BP levels (P<0.05). These subjects also presented an exaggerated BP response during the cold pressor test. These results support the notion of an integrated pattern of cardiac and vascular adaptation during the development of hypertension

Diverse effects of renal denervation on ventricular hypertrophy and blood pressure in DOCA-salt hypertensive rats

Cardiac hypertrophy that accompanies hypertension seems to be a phenomenon of multifactorial origin whose development does not seem to depend on an increased pressure load alone, but also on local growth factores and cardioadrenergic activity. The aim of the present study was to determine if sympathetic renal denervation and its effects on arterial pressure level can prevent cardiac hypertrophy and if it can also delay the onset and attenuate the severity of deoxycorticosterone acetate (DOCA)-salt hypertension. DOCA-salt treatment was initiated in rats seven days after uninephrectomy and contralateral renal denervation or sham renal denervation. DOCA (15 mg/kg, sc) or vehicle (soybean oil, 0.25 ml per animal) was administered twice a week for two weeks. Rats treated with DOCA or vehicle (control) were provided drinking water containing 1 percent NaCl and 0.03 percent KCl. At the end of the treatment period, mean arterial pressure (MAP) and heart rate measurements were made in conscious animals. Under ether anesthesia, the heart was removed and the right and left ventricles (including the septum) were separated and weighed. DOCA-salt treatment produced a significant increase in left ventricular weight/body weight (LVW/BW) ratio (2.44 + 0.09 mg/g) and right ventricular weight/body weight (RVW/BW) ratio (0.53 + 0.01 mg/g) compared to control (1.92 + 0.04 and 0.48 + 0.01 mg/g, respectively) rats. MAP was significantly higher (39 percent) in DOCA-salt rats. Renal denervation prevented (P>0.05) the development of hypertension in DOCA-salt rats but did not prevent the increase in LVW/BW (2.27 + 0.03 mg/g) and RVW/BW (0.52 + 0.01 mg/g). We have shown that the increase in arterial pressure level is not responsible for cardiac hypertrophy, which may be more related to other events associated with DOCA-salt hypertension, such as an increase in cardiac sympathetic activity.

Neural reflex regulation of arterial pressure in pathophysiological conditions: interplay among the baroreflex, the cardiopulmonary reflexes and the chemoreflex

The maintenance of arterial pressure at levels adequate to perfuse the tissues is a basic requirement for the constancy of the internal environment and survival.The objective of the present review was to provide information about the basic relfex mechanisms that are responsible for the moment-to-moment regulation of the cardiovascular system. We demonstrate that this control is largely provided by the action of arterial and non-arterial reflexes that detect and correct changes in arterial pressure (baroreflex), blood volume or chemical composition (mechano-and chemosensitive cardiopulmonary reflexes), and changes in bloodgas composition (chemoreceptor reflex). The importance of the integration of these cardiovascular reflexes is well understood and it is clear that processing mainly occurs in the nucleus tractus solitarii, although the mechanism is poorly understood.There are several indications that the interactions of baroreflex, chemoreflex and Bezold-Jarisch reflex inputs, and the central nervous system control the activity of autonomic preganglionic neurons through parallel afferent and efferent pathways to achieve cardiovascular homeostasis. It is surprising that so little appears in the literature about the integration of these neural reflexes in cardiovascular function. Thus, our purpose was to review the interplay between peripheral neural reflex mechanisms of arterial blood pressure and blood volume regulation in physiological and pathophysiological states. Special emphasis is placed on the experimental model or arterial hypertension induced by N-nitro-L-arginine methyl ester (L-NAME) in which the interplay of these three reflexes is demonstrable.

Efeitos da administração crônica do álcool sobre os mecanismos neurais de regulação da pressão arterial / Effect of Chronic Administration of Alcohol and its Withdrawal on the Neural Mechanisms of Arterial Blood Pressure Regulation

PURPOSE: This study evaluated the effect of alcohol and its withdrawal on arterial baroreflex (BR) and cardiopulmonary reflex (CPR). METHODS: Male Wistar rats (150-250g) distributed in three groups (10-19 animals in each): ETOH 0, ETOH 5and ETOH 20, received alcohol solution at the end of the day and at night over the week, and all day and night at the weekends for a 90 day period. The BR function was assessed analyzing the bradycardic response to phenylephrine-induced vasoconstriction and tachycardic response to sodium nitroprusside-induced vasodilatation. The CPR was evaluated through the simultaneous bradycardic and hypotensive responses to 5-hydroxytryptamine (5-HT). The tests were performed in conscious animals in conditions of alcohol intake or 48h alcohol withdrawal. RESULTS: The nonwithdrawn animals of ETOH 5group showed significative decrease of mean arterial pressure compared to ETOH 0and an increase of heart rate compared to ETOH 0and 20groups. The sensitivity (gain) of baroreceptor reflex was significantly attenuated in ETOH 5withdrawn animals and in ETOH 5and 20animals nonwithdrawn. This was mainly due to the reduction of range of the baroreflex and changes in the bradycardia and tachycardia plateau. The nonwithdrawn ETOH 5group showed a higher effect of 5-HT (around 50) on the fall of diastolic arterial pressure. CONCLUSION: These results suggest that alcohol intake produced significant alterations in the neural mechanisms of cardiovascular regulation that could result in a dysfunction of blood pressure regulation.

Exaggerated Bezold-Jarisch reflex in the hypertension induced by inhibition of nitric oxide synthesis

The present study was designed investigate the role of cardio-pulmonary reflex, more specifically the bezold-Jarisch reflex, in experimental hypertension induced by chronic administration of Nw-nitro-L-arginine methyl ester (L-NAME) (0,5 mg/ml) added to the drinking water for 6 days. The study was perfomed in male Wistar rats (200-350 g), 9 animals per group. L-NAME ingestion caused a significant increase in resting mean arterial pressure (MAP: 182 + or - 4mmHg) and heart rate (HR: 447 = or - 20 bpm) when compared to untreated rats (MAP: 112 = or - 3 mmHg and HR: 355 + or - 10 bpm). Cardiopulmonary receptors were chemically stimulated with bolus injections of 5-hydroxytryptamine (5-HT, 4-10 ug/Kg, iv) followed by measuring the falls in diastolic arterial pressure (DAP) and HR in conscious and freely moving animals. An expected, the responses to intravenous injections of 5-HT consisted of a dose-dependent reduction in HR (from 26 = or - 14 to 175 + or - 25 bpm) and DAP (from 7 + or - 4 to 39 + or - 3 mmHg) in the control rats. Both bradycardia and diastolic hypotension were significantly accentuated in the L-NAME animals (approximately 30 per cent). These data suggest that, in contrast to other models of hypertension, in the present one caused by inhibition of nitric oxide synthesis, the Bezold-Jarisch reflex exaggerated. This neural dysfunction could be related to changes in the cardiac vagal effrent or effector

Calpain activity of hypertrophic hearts from hypertensive rats

Heart tissue contains large amounts of the Ca²+ -activated protein-ase calpain which has been assigned a specific function in the turnover of muscle protein. The objective of the present study was to determine calpain (E.C. 3.4.22.17)-like activity in homogenates of left ventricle from hypertensive rats that developed ventricular hypertrophy. Calpain activity was assayed using heat-denaturated azocasein as a substrate in the presence of 1 mM calcium and corrected by subtraction of the Ca²+ -independent activities. Tha latter were measured in the presence of 1 mM EGTA and the products read at 440nm. Male Wistar rats (225g) were assgned to control (N=8, normal drinking water), salt (N=6, drinking water containing 1 percent NaCl) and DOCA-salt (N=6, deoxycorticosterone acetate, 8 mg/Kg, sc, twice a week for 20 days plus drinking water containing 1 percent NaCl) groups. SHR (N =6, spontaneously hypertensive rats) were also used. The calpain activity of the control group was at 3.90 ñ 0.22 mU/g wet weight tissue. Hypertension induced significant left ventricular hypertrophy in DOCA-salt rats (26 percent) and in SHR (54 percent) and a 30 percent decrease in calpain activity in both groups (P < 0.01). In the high salt load (salt group) calpain activity was also decreased, but this was not accompanied by hypertrophy...

Heart prolyl endopeptidase activity in one-kidney, one clip hypertensive rats

1. Heart mass, prolyl endopeptidase activity and fractionated proteins from heart tissue were studied in one-kidney, one clip hypertensive rats (N=6) and compared to sham-operated rats (N=6). 2. Body weigh, arterial pressure and tissue mass were measured 4 weeks after artery clipping Z-Gly-Pro-p-nitroaniline hydrolysis was used to measure tissue prolyl endopeptidase activity in the homogenate. Protein was fractionated into the soluble and myofibrillar fractions. 3. In the normotensive rats, prolyl endopeptidase activity expressed in terms of protein specific activity (µM substrate hydrolyzed h-1 mg supernatant protein-1) occurred in atria and was 2.5-fold higher than in the ventricles (3.79 ñ 0.20 vs 1.44 ñ 0.02, P<0.05). In the one-kidney, one clip hypertensive rats, the left ventricle tissue increased 1.7-fold (2.27 ñ 0.11 vs 3.72 ñ 0.11 mg wet weight tissue/g body weight, P<0.001), the soluble protein fraction (54.86 ñ 3.60 vs 57.38 ñ 6.64 mg/g wet weight tissue) was unchanged, while the myofibrillar fraction increased 1.9-fold (118.9 ñ 9.09 vs 229.8 ñ 8.47 mg/g wet weight tissue, P<0.001). 4 The specific activity of the atrial and ventricular prolyl endopeptidase decreased in atria and increased in ventricles as the result of hypertension (3.79 ñ 0.2 vs 2.84 ñ 0.13 and 1.44 ñ 0.02 vs 1.87 ñ 0.13; respectively). These regional differences in prolyl endopeptidase enxyme content caused by one-kidney, one clip hypertension in neurosecretory and non-neurosecretory heart areas suggest that this enzyme plays a local role in the turnover of specific polypeptides

Sigmoidal curve-fitting of baroreceptor sensitivity in renovascular 2K1C hypertensive rats

The time course of changes in baroreceptor reflex sensitivity in Goldblatt two-kidney one clip (2K1C) hypertension was studied 3, 7 and 30 days after renal artery clipping by means of a sigmoidal curve-fitting analysis. Experiments were performed in 54 adult male Wistar rats (N = 9 per group) weighing 200-300 g. The reflex heart rate responses were elicited by alternate intravenous bolus injections of phenylephrine (delta +5 to +50 mmHg) and sodium nitroprusside (delta -5 to -50 mmHg). A clear upper and lower plateau (reflex tachycardia and bradycardia, respectively) was noted in both sham and hypertensive groups. Although the resting mean arterial pressure was significantly increased in all hypertensive groups (131 +/- 3, 149 +/- 7 and 168 +/- 11 mmHg, respectively, 3, 7 and 30 days after clipping), when compared to the sham group (108 +/- 2 mmHg), significant changes in baroreceptor reflex function were observed only in 7- and 30-day groups. Baroreflex sensitivity was markedly reduced in these hypertensive rats (2.3 +/- 0.3 and 1.9 +/- 0.3 bpm/mmHg, respectively) compared to the sham group (4.2 +/- 0.3 bpm/mmHg). In addition, a reduced baroreflex heart rate range was observed in these groups (117 +/- 12 and 107 +/- 10 bpm, respectively) compared to the sham group (165 +/- 11 bpm). These data indicate an impairment of baroreflex function in conscious 2K1C hypertensive rats which seems to be secondary to arterial hypertension.

Contribution of the cardiopulmonary reflex to the cardiovascular regulation in normal and pathophysiological states

1. The existence of inhibitory vagal reflexes arising from cardiac and pulmonary receptors has been recognized for over a century. The cardiopulmonary region contains numerous receptors whose unmyelinated afferent fibers course in the vagus nerves and appear to exert a tonic influence on medullary areas related to heart beat and vasomotor activity. Studies on experimental animals and humans indicate that cardiopulmonary reflexes play an important role in blood pressure and blood volume control. 2. Experimental approaches include a selective decrease or increase of cardiopulmonary receptor activity by reducing or increasing central venous pressure in man, and stimulation of chemosensitive cardiac vagal endings in animals. These studies indicate that the inhibitory cardiopulmonary reflex function is altered in experimental and clinical hypertension. The cardiopulmonary dysfunction in hypertensive disease appears to be related to cardiac structural alterations secondary to the hypertensive state.

Impairment of the Bezold-Jarisch reflex in conscious rats with myocardial hypertrophy

The aim of the present investigation was to study the Bezold-Jarisch reflex in catecholamine-induced myocardial hypertrophy. Ten conscious male albino rats (260-300 g) were treated for 15 days with isoproterenol (IR), 0.3 mg/kg injected im once a day, and compared to 10 control rats (CR) similarly injected with vehicle (0.25 ml). No significant changes in body weight, resting mean arterial pressure or heart rate were observed in the IR group. Left and right ventricular hypertrophy was observed in IR animals (27 and 28, respectively, P < 0.01) when compared to CR. The Bezold-Jarisch reflex was tested by injecting 5-hydroxytryptamine (4-32 micrograms/kg, iv) and was characterized by a simultaneous fall in diastolic arterial pressure (for example: 91 +/- 4 to 61 +/- 3 mm Hg, 16 micrograms/kg) and bradycardia (for example: 330 +/- 10 to 177 +/- 25 bpm, 16 micrograms/kg). This reflex was significantly attenuated in the IR when compared to the CR group. Our data suggest that ventricular hypertrophy without changes in arterial pressure can lead to a reduction of the Bezold-Jarisch reflex. The results reported here are in agreement with other studies showing that the impairment of cardiopulmonary reflex in hypertensive animals and humans occurs exclusively when the hypertension is accompanied by ventricular hypertrophy.

Baroreceptor reflex function in rats submitted to chronic inhibition of nitric oxide synthesis

1. The chronic inhibition of nitric oxide synthesis by N omega-nitro-L-arginine-methyl ester (L-NAME) leads to arterial hypertension accompanied by a significant increase in cardiac sympathetic tone and an almost complete abolition of the vagal tone in conscious adult male Wistar rats. The main aim of the present study was to examine the baroreceptor heart rate reflex function in L-NAME-treated rats (N = 10). 2. Spontaneous daily oral intake of L-NAME (1 mg/ml for 6 days) caused marked hypertension and tachycardia (176 +/- 5 mmHg and 418 +/- 16 bpm), when compared to untreated rats (111 +/- 2 mmHg and 354 +/- 8 bpm). 3. Baroreflex gain was determined in conscious freely moving rats by sigmoidal curve fitting analysis using alternate intravenous injections of phenylephrine (0.2-10.0 micrograms/kg) and sodium nitroprusside (0.5-20.0 micrograms/kg) to produce pressor-induced bradycardia and depressor-induced tachycardia, respectively. The baroreflex gain (sensitivity) was significantly enhanced in L-NAME-treated rats compared to control rats (10.9 +/- 2.5 vs 4.5 +/- 0.3 bpm/mmHg, respectively) mainly due to exaggerated reflex bradycardia responses to increases in arterial hypertension. 4. The data indicate that chronic inhibition of nitric oxide synthesis enhances the bradycardic component of the baroreflex function

Cardiovascular effects on conscious rats of pretreatment with isoproterenol for 3 days

The cardiovascular effect of of isoproterenol pretreatment (ISO) mimicking short duration sympathetic hyperacitivity was studied in conscious adult male albino rats. Cardiac hypertrophy of right and left ventricles was observed after pretreatmewnt with isoproterenol for 3 days (0.1 mg/kg, 3 times a day). when compared to saline-treated rats. The pressor response to noradrenaline (NOR, 1 to 1000 ug/kg, iv) was slightly but consistently larger in the ISO group than in the control group (in mm Hg, Control = 109 ñ 3.5; NOR 1 = 114 ñ 3.3; NOR 10=116 ñ 4: NOR 100 = 127 ñ 5.6 and NOR 1000 = 152 ñ 7.3 for saline-treated rats and, Control = 106 ñ 5.1; NOR 1 = 112 ñ 5.1; NOR 10 = 118 ñ 5.3; NOR 100 = 134 ñ 4.9 and NOR 1000 = 162 ñ 7.5 for ISO groups). An increased reflex bradycardia was also observed in response to increasing doses of noradrenaline (in bpm, Control = 323 ñ 5.6; NOR 1 = 313 ñ 6.8; NOR 10 = 309 ñ 8.6; NOR 100 = 293 ñ 7.5 and NOR 1000 = 284 ñ 5.3 for saline-treated rats and Control = 316 ñ 4.3; NOR 10 = 289 ñ 3.4; NOR 100 = 267 ñ 4 and nor 1000 = 251 ñ 2.6 for ISO groups; ANOVA, P<0.01). There were no significant differences autonomic tone to the heart between control and isoproterenol-pretreated animals. The present results indicate that isoproterenol treatment induces significant in vivo cardiovascular modifications

Captopril prevents ventricular hypertrophy in sinoaortic denervated rats

We had previously reported that sinoaortic denervation induces cardiac ventricular hypertrophy in rats. The objective of the present study was to determine whether this cardiac hypertrophy can be prevented by inhibition of angiotensin converting enzyme (ACE) with captopril, 20 mg/kg, administered sc twice daily for 15 days. The left ventricular weight/body weight ratio significantly increased (12%) in sinoaortic denervated (SAD) rats 15 days after surgery when compared with the sham-operated group (SO). Administration of captopril to SAD rats prevented this ventricular hypertrophy and decreased but did not completed abolish their high arerial pressure. No changes in the normal pattern of baroreceptor reflex activity were observed in the captopril-pretreated SAD or SO groups. These data suggest the participation of the angiotensin system in the development of cardiac hypertrophy in SAD rats