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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 g 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.

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.

The mouse is the most used animal for studying the genetic basis of cardiovascular diseases. However, the mechanisms of regulation of cardiovascular function in this animal are not yet well understood. The goal of this study was to evaluate the baroreflex, the Bezold-Jarisch cardiopulmonary reflex (BJR), and the chemoreflex in mice with hypertension induced by inhibition of NO using Nomega-nitro-L-arginine-methyl ester (L-NAME). Basal mean arterial pressure (MAP) measured under anesthesia (urethane, 1 mg/g IP) was significantly higher in L-NAME (400 microgram/g IP for 7 days)-treated (HT) mice (n=7) compared with vehicle-treated (NT; n=10) animals (126+/-9 versus 79+/-2 mm Hg) without differences in heart rate (HR). Baroreflex sensitivity, evaluated using phenylephrine (1 microgram/g IV) was enhanced in HT mice compared with NT mice (-9.8+/-1.4 versus -4.9+/-0.5 bpm/mm Hg). The BJR, induced by phenylbiguanide (40 ng/g IV), was significantly attenuated in HT animals (MAP, -13+/-5%; HR, -39+/-6%) compared with NT animals (MAP, -38+/-5%; HR, -66+/-2%). The chemoreflex, induced by potassium cyanide (0.26 microgram/g IV), was significantly attenuated in HT animals (MAP, +14+/-4%; HR, -8+/-2%) compared with NT animals (MAP, +29+/-4%; HR, -15+/-4%). As has been observed in rats, chronic inhibition of NO synthase in mice results in arterial hypertension. Enhancement of baroreflex sensitivity and attenuation of BJR and chemoreflex seem to be mainly caused by inhibition of NO synthesis because individual analyses did not show positive correlation between changes in these reflexes and MAP levels in the HT group.

The contributions of arterial baroreceptor and Bezold-Jarisch reflexes, and atrial natriuretic factor (ANF) to the anti-hypertensive effect of the diuretic chlorthalidone were investigated in rats with deoxycorticosterone acetate (DOCA)-salt-induced hypertension. Chlorthalidone (8 mg rat(-1)day(-1)added to food) was given to one group during all 20 days of DOCA (8 mg kg(-1)s.c. twice per week) administration (preventive regimen) and, to another group, 20 days after DOCA treatment was initiated until the 40th day (therapeutic regimen). DOCA caused a significant increase in mean arterial pressure, reduced arterial baroreflex, and increased both the Bezold-Jarisch reflex and pro-ANF converting enzyme activity. Chlorthalidone reversed or prevented the DOCA-salt-induced hypertension, which was accompanied by the normalization of both the arterial baroreflex and the Bezold-Jarisch reflex. Additionally, both preventive and therapeutic regimens with chlorthalidone did cause normalization of the plasma sodium concentration and pro-ANF converting enzyme activity in the left atrium that follows DOCA-salt hypertension. Although it is difficult to determine the relative importance of each of the above regulatory mechanisms altered by chlorthalidone treatment, these data indicate that they may account for the prevention or decrease of DOCA-salt-induced hypertension in rats., (Copyright 2000 Academic Press.)

There are clinical and experimental evidences that the cardiopulmonary reflex function is impaired in chronic hypertension, but it could be due to myocardial hypertrophy rather than to hypertension itself. To test this hypothesis we evaluated the Bezold-Jarisch reflex in experimental conditions of myocardial hypertrophy and arterial normotension. Adult male Wistar rats were subjected to myocardial hypertrophy (MHR) treating them with the beta-adrenoceptor agonist isoproterenol (0.3 mg/kg/day, s.c.) for 15 days and compared with vehicle injected control rats (CR). No significant changes in body weight (283+/-14 vs. 299+/-9 g), resting mean arterial pressure (104+/-4 vs. 110+3 mm Hg) or heart rate (330+/-11 vs. 358+/-18 bpm) were observed in MHR compared to CR. As expected, MHR showed left and right ventricular and left atrial hypertrophy when compared to CR. The bradycardia and hypotension that characterizes the Bezold-Jarisch reflex, induced by the 5-HT3, agonist phenyldiguanide (1.5-24.0 microg/kg, i.v.), were significantly decreased in MHR compared to CR. Cardiac muscarinic responsiveness, which was assessed by electrical stimulation of the efferent vagus in anesthetized animals or by stimulation of muscarinic receptors in isolated hearts, was unchanged or increased, respectively, in MHR compared to CR. Additional studies showed that the baroreflex and chemoreflex were also attenuated in MHR compared to CR. These data indicate that cardiac hypertrophy impairs the Bezold-Jarisch reflex probably due to changes at central integrative areas of the reflex.

The Bezold-Jarisch reflex function was evaluated in rats made hypertensive by the chronic oral intake of a nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, averaging 35 mg/kg/day), for 3, 6, and 12 days (n = 9/group) and in untreated control rats (CR, n = 9/group). L-NAME-treated rats showed a marked hypertension (MAP: 148 +/- 3, 182 +/- 4, and 179 +/- 4 mm Hg, respectively) compared with CR (110 +/- 2 mm Hg). The 6- and 12-day groups showed tachycardia (447 +/- 20 and 466 +/- 13 beats/min, respectively) when compared with CR (355 +/- 10 beats/min). When compared with CR, left ventricular hypertrophy was observed in rats treated with L-NAME for 6 and 12 days. The Bezold-Jarisch reflex, a decrease in heart rate (HR) accompanied by a decrease in diastolic arterial pressure (DAP), was evoked in a dose dependent manner by the intravenous injection of 5-hydroxytryptamine (5-HT, 5 to 10 microg/kg). Relative to responses observed in CR, 5-HT at 10 microg/kg caused a four- to fivefold greater decrease in HR and a two- to threefold greater decrease in DAP in all the L-NAME treatment groups. Using a Langendorff technique, we observed a significant increase in the responsiveness of the pacemaker to acetylcholine (1.25 to 80 microg/mL). These data suggest that the pharmacological inhibition of the nitric oxide synthase causes profound changes in the mechanisms of cardiovascular regulation as shown by a marked enhancement of the Bezold-Jarisch reflex in L-NAME-treated rats. The enhancement of this reflex seems to be in great part due to the hyperresponsiveness of the cardiac pacemaker to cholinergic stimulation.

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 reflex 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 blood-gas 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 of arterial hypertension induced by N-nitro-L-arginine methyl ester (L-NAME) in which the interplay of these three reflexes is demonstrable.

Purpose: To evaluate the levels of blood pressure when measured by casual and ambulatory blood pressure monitoring., Methods: We studied 16 sedentary and normotensive subjects (mean 43 +/- 3 years old) showing an exaggerated blood pressure response (SBP > 220 mmHg) during a cycloergometric test, hyperreactive group (HG). This group was compared to 15 others with SBP < or = 220 mmHg during exercise, normoreactive group (NG). Casual blood pressure was obtained by the conventional method and the ambulatory blood pressure monitoring (ABPM) was obtained with SpaceLabs 90207 monitor. This procedure (test 1) was repeated after four months (test 2)., Results: Both groups showed statistically higher levels of blood pressure when measured by ABPM device, compared to casual measurements. Systolic blood pressure was significantly higher in HG in casual measurement, in test 1 but not in test 2. Diastolic blood pressure was significantly higher in HG only through the ABPM device. The ambulatory blood pressure average values for two or 24 hours was similar in both groups. No significant differences were observed in left ventricular morphology at the echocardiogram., Conclusion: These findings indicate that hyperreactive subjects have an exaggerated stress-induced cardiovascular response during the installation of the device.

This study was carried out to test the effect of chlorthalidone (Chlor) treatment on the vascular responsiveness to acetylcholine (Ach) and adenosine disphosphate (ADP) under different extracellular calcium concentrations (Cae2+) in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Half of the DOCA-salt hypertensive rats were simultaneously given Chlor (8 mg day-1, p.o.), after the twentieth day of DOCA, until the fortieth day. Mean arterial pressure (MAP) was reduced (P < 0.01) in DOCA-salt-Chlor (121 +/- 3 mmHg) compared to DOCA-salt (175 +/- 3 mmHg) rats. Chlor reduced the high plasma sodium of DOCA-salt to levels of the normotensive groups. The basal perfusion pressure of the isolated mesenteric vascular bed (MVB) was not modified by Cae2+ changing or previous addition of ouabain. At normal and low Cae2+ the vasodilator effect of Ach in the MVB was reduced (P < 0.01) in DOCA-salt and less (P < 0.05) in the salt-control rats. Chlor shifted the curve of DOCA-salt backward to control group curves. In high Cae2+ the vasodilator responses to Ach were reduced (P < 0.01) both in normal-control and DOCA-salt+Chlor but not in salt-control but not in salt-control and DOCA-salt group. The vasodilator effect of ADP to different Cae2+ was similar in presence of normal and low Cae2+ in normal-control rats and it was reduced (P < 0.01) in presence of high Cae2+ in the DOCA-salt group. Chlor restored the responses to ADP to normal-control level. Under ouabain-treatment, the vasodilation duration was reduced (P < 0.05) in all groups. It was shorter (P < 0.01) in DOCA-salt than in the other ones. Chlor completely abolished this difference. The MAP reduction in DOCA-salt rats by chlor could also be associated with a restored normal responsiveness of endothelial cells to endogenous vasodilator, for example Ach and ADP, since sodium nitroprusside did not exhibit differences among the various treatments. This diuretic agent seems to elicit its effect through a reduction in plasma sodium content of DOCA-salt hypertensive rats.

It is possible that behavioral dysfunction, including cognitive, perceptual and psychomotor impairments in hypertensive subjects, can be the result of the high blood pressure. The aim of this study was to evaluate the performance of the spontaneously hypertensive rats (SHR) in the acquisition and execution of tasks in an 8-arm radial maze. Male Wistar normotensive rats (CON, n = 11) and SHR (n = 12), 3 months old, were first submitted to a series of training sessions to enter each of the 8 arms once in a given session (task acquisition), and errors (revisiting an arm in the same session) were computed. Errors before and after two delay intervals (5 s and 1 h, introduced between the fourth and fifth arm choice) were measured. These delayed tests allowed us to evaluate the working memory in different terms. It was observed that the SHR group made slightly more errors during the acquisition sessions and in the execution of the post-delay of 5-s interval tests, and significantly in the execution of the post-delay of 1-h interval tests compared to the CON. These results show that the SHR has a deficiency in the performance of the radial maze, suggestive of impairment of learning and working memory, mainly for a long-term memory, corroborating the hypothesis about the possible behavioral consequences of hypertension.

We performed experiments to study the effects of electrolytic lesions of periaqueductal gray matter on mean blood pressure, heart rate, and cardiac baroreflex in adult male spontaneously hypertensive rats. Cardiac baroreflex was assessed by the administration of randomly assigned doses of phenylephrine (0.3 to 5.0 micrograms/kg i.v.) or sodium nitroprusside (1.5 to 5.0 micrograms/kg i.v.) to unanesthetized rats. Bilateral lesions of the periaqueductal gray matter (0.5 mA/5 s) were then performed with rats under sodium pentobarbital anesthesia (35 mg/kg i.p.). Twenty hours after lesion, cardiac baroreflex was retested. Baroreflex data were analyzed by sigmoidal curve fitting. Lesion rats (n = 12) showed a significant decrease in both the gain (delta = -0.89 +/- 0.38 beats per minute [bpm]/mm Hg, P < .05) and curve midpoint (delta = -15 +/- 6 mm Hg, P < .05) of the cardiac baroreflex. Moreover, despite a moderate increase in heart rate (delta = 34 +/- 10 bpm, P < .01), resting mean blood pressure was significantly decreased 24 hours after the lesions (delta = -19 +/- 5 mm Hg, P < 01). No significant changes in cardiac baroreflex were observed in sham-lesion rats (n = 12). Histological examination showed circumscribed bilateral damage of dorsolateral periaqueductal gray matter. Dorsolateral periaqueductal gray matter is an area of the brain putatively related to fear and anxiety. It also projects onto premotor sympathetic neurons in the medulla. Although electrolytic lesions damage neurons as well as fibers of passage, these data suggest that dorsolateral periaqueductal gray matter has a far greater influence on resting cardiovascular control in spontaneously hypertensive rats than was previously suspected.

The present study was designed to investigate the role of cardiopulmonary 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 performed 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 +/- 4 mmHg) and heart rate (HR: 447 +/- 20 bpm) when compared to untreated rats (MAP: 112 +/- 3 mmHg and HR: 355 +/- 10 bpm). Cardiopulmonary receptors were chemically stimulated with bolus injections of 5-hydroxytryptamine (5-HT, 4-10 micrograms/kg, iv) followed by measuring the falls in diastolic arterial pressure (DAP) and HR in conscious and freely moving animals. As expected, the responses to intravenous injections of 5-HT consisted of a dose-dependent reduction in HR (from 26 +/- 14 to 175 +/- 25 bpm) and DAP (from 7 +/- 4 to 39 +/- 3 mmHg) in the control rats. Both bradycardia and diastolic hypotension were significantly accentuated in the L-NAME animals (approximately 30%). 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 is exaggerated. This neural dysfunction could be related to changes in the cardiac vagal efferent or effector.

Neurogenic hypertension results from the removal of inhibitory baroreceptor afferent input to vasomotor systems in the central nervous system. We sought to determine whether the bilateral destruction of neurons in the rostral ventrolateral or rostral ventromedial medulla, made using microinjections of N-methyl-D-aspartic acid (30 nmol in 200 nL), would block the acute increase in arterial pressure after sinoaortic deafferentation in pentobarbital-anesthetized rats. Bilateral lesions of the rostral ventrolateral or rostral ventromedial medulla decreased mean arterial pressure (107 +/- 4 to 78 +/- 5 and 115 +/- 3 to 94 +/- 3 mm Hg, respectively). In rostral ventrolateral or rostral ventromedial medulla lesioned rats, sinoaortic deafferentation failed to increase arterial pressure. Sham lesions or lesions placed rostral to the rostral ventrolateral or rostral ventromedial medulla did not significantly lower arterial pressure. Subsequent sinoaortic deafferentation significantly increased mean arterial pressure (109 +/- 3 to 145 +/- 4 and 109 +/- 5 to 141 +/- 3 mm Hg, respectively). In eight rats we used an infusion of angiotensin II to return arterial pressure to control levels after lesion of the rostral ventrolateral (n = 4) or rostral ventromedial (n = 4) medulla. In these animals, sinoaortic deafferentation failed to increase arterial pressure. We conclude that neurons in the rostral ventrolateral and rostral ventromedial medulla are involved in the normal maintenance of arterial pressure and the development of hypertension after sinoaortic deafferentation in pentobarbital-anesthetized rats.

Diuretics have been the mainstay of long-term treatment of hypertension, but there is no evidence suggesting that diuretics may be effective in reducing cardiac hypertrophy associated with hypertension. Thus, the present study was carried out to elucidate if long-term treatment with chlorthalidone (8 mg per animal per day added to food) affects the development of and reverses the ventricular hypertrophy in deoxycorticosterone acetate (DOCA) (8 mg/kg SC twice a week)-salt hypertensive rats. Chlorthalidone was given to one group during all 20 days of DOCA administration (preventive regimen) and to another group 20 days after DOCA treatment was initiated until the 40th day (therapeutic regimen). Chlorthalidone was found to reduce or prevent the development of ventricular hypertrophy, as assessed by a reduction in ventricular mass and cardiac protein as well as arterial hypertension. Both chlorthalidone regimens prevented the increase or induced a significant decrease in the plasma concentration of sodium and in cardiac sympathetic tone, which were both increased in DOCA-salt-treated rats. These data provide evidence that long-term chlorthalidone treatment is effective in preventing or reducing ventricular hypertrophy along with arterial hypertension. However, whether this is due to a reduction in plasma sodium or other additional mechanisms, such as a reduction in cardiac sympathetic tone, remains to be determined.

The present study was designed to investigate the role of the autonomic nervous system in experimental hypertension induced by chronic administration of N-nitro-L-arginine methyl ester (L-NAME) in the drinking water (1 mg/mL) over 6 days. L-NAME ingestion caused a large rise in resting mean arterial pressure (MAP) (175 +/- 5 mm Hg) and heart rate (HR) (440 +/- 17 beats per minute) compared to nontreated control rats (resting MAP: 112 +/- 2 mm Hg and HR: 345 +/- 8 beats per minute). Ganglionic blockade induced by trimethaphan (5 mg/kg, intravenously) caused a significantly (P < .01) greater decrease in MAP (delta -86 +/- 7 mm Hg) compared to control rats MAP (delta -44 +/- 4 mm Hg). This strongly suggests that the level of central sympathetic tone in L-NAME-treated rats is much greater than in nontreated rats. Using atenolol and atropine alone and combined, the level of resting sympathetic drive to the heart was found to be significantly increased in L-NAME-treated rats compared to control rats. However, vagal tone to the heart was found to be virtually abolished in L-NAME-treated rats compared to control rats. These results indicate that an increase in central sympathetic drive plays an important role in the hypertension induced by chronic inhibition of nitric oxide synthesis with L-NAME.

The mechanisms of anti-hypertensive effect of diuretics remain unknown. The purpose of this study was to test the hypothesis that long-term treatment with chlorthalidone decreases the responsiveness of resistance vessels to neurohormones. The study was performed in deoxycorticosterone acetate (DOCA)-salt hypertensive rats with and without treatment with chlorthalidone (Chlor. 8 mg/day, for 20 days). Resting mean arterial pressure in freely moving state was significantly reduced in DOCA-salt-Chlor rats when compared to DOCA-salt rats (116 +/- 3 vs 147 +/- 7 mmHg, respectively). Chlorthalidone treatment reduced the high plasma sodium content observed in DOCA-salt rats to the same levels observed in normotensive control groups. Results obtained in isolated perfused mesenteric arteries showed: a) the increase in perfusion pressure elicited by norepinephrine (NE), serotonin (SE) and vasopressin (VP) was significantly greater in DOCA-salt than in DOCA-salt + Chlor rats or control normotensive rats; b) the endothelium removal increased the pressor responses to NE, SE and VP in a similar way in all groups. These data provide evidence that long-term chlorthalidone treatment reduces vascular hyperresponsiveness to these neurohormones. In addition, these results indicate that this reduction in vascular hyperresponsiveness, associated with a decrease in extracellular sodium level, could be a possible mechanism by which the diuretics reduce the high blood pressure.

A large body of evidence indicates that the central nervous system plays an essential role in the pathogenesis of hypertension. However, in many cases the specific brain regions involved and the mechanisms by which these regions promote hypertension are not known. In recent years, research in this and other laboratories has attempted to determine the mechanisms by which neural and humoral signals arising in response to pathological conditions (often occurring in the periphery) interact with the central nervous system to produce hypertension. In this article, we illustrate the coupling of peripheral and central factors in the pathogenesis of hypertension by examining the central actions of angiotensin II and mineralocorticoids in the expression of renal hypertension and mineralocorticoid-salt hypertension, respectively. We also review recent data from this laboratory illustrating the involvement of medullary vasomotor centers in the development of neurogenic hypertension after sinoaortic deafferentation and in the maintenance of hypertension in the spontaneously hypertensive rat.

Hypertension caused by deoxycorticosterone-salt (DOC-salt) may involve enhanced sympathetic tone and some diuretics may exert their antihypertensive action by modulating presynaptic adrenergic sensitivity. This study analyzes the noradrenergic sensitivity of the perfused mesentery isolated from DOC-salt hypertensive rats treated or not with chlorthalidone. Chlorthalidone treatment reduced arterial hypertension in DOC-salt treated rats (from 160 +/- 7 to 127 +/- 5 mmHg). The diuretic completely prevented the increase in sympathetic tone and blunted the decreased vagal tone observed in DOC-salt rats. Norepinephrine-induced vasoconstriction was enhanced in perfused mesenteries isolated from DOC-salt rats. This alteration was attenuated in preparations from chlorthalidone-treated DOC-salt animals. Blockade of neuronal catecholamine uptake using cocaine did not change these responses. These data suggest that chlorthalidone reduces the vascular hyperresponsiveness to catecholamines observed in DOC-salt treated hypertensive rats.

The effects of verapamil (220 micrograms/kg per min i.v.) on blood pressure and heart rate were studied in sinoaortic baroreceptor denervated and sham-operated rats. In the conscious animals the verapamil-induced hypotension was accompanied by a significant heart rate increase in the first group (from 352 +/- 7 to 422 +/- 10 beats/min) and a decrease in the second group (from 485 +/- 13 to 400 +/- 9 beats/min). The verapamil-induced tachycardia observed in sham-operated rats was prevented by atropine plus propranolol but not by adrenal demedullation. Tachycardia was present in urethane-anesthetized sham-operated rats, similar to the sinoaortic baroreceptor-denervated rats. After verapamil a significant heart rate reduction was observed in sham-operated but not in sinoaortic baroreceptor-denervated rats. The results in conscious rats suggest that the direct inhibitory action of this drug on sinus node automaticity is suppressed by baroreflex tachycardia and that anesthesia masks this response.

The effects of nifedipine (15 micrograms/kg, i.v.) on mean blood pressure (MBP) and heart rate were studied in neurogenic hypertensive rats (NHR), compared with renovascular hypertensive (RHR), and control (CR) rats. The maximal MBP reduction reached 32, 37 and 9%, respectively. The baseline MBP was recovered after 120, 150, and 5 min, respectively. The hypotension was not accompanied by changes in the baseline high heart rate of NHR and by tachycardia in CR and RHR groups. The data show the antihypertensive efficacy of nifedipine in both models of hypertension and indicate that under conditions of increased sympathetic tone the cardiac pacemaker cannot be easily inhibited by nifedipine.

The influence of sex hormones on the development of left ventricular hypertrophy was investigated in baroreceptor-denervated rats. A significant increase (p less than 0.01) in the left ventricular weight/body weight ratio was observed in male but not in female rats 15 days after operation, compared to age- and sex-matched sham-operated rats. This differential hypertrophy occurred despite the development of a significant elevation in arterial blood pressure in both sexes. Castration prior to sinoaortic denervation did not change the level of arterial hypertension but caused a significant reduction (p less than 0.01) in left ventricular weight in male rats and a significant increase (p less than 0.01) in female rats. The pretreatment of male and female sinoaortic denervated and castrated rats with testosterone resulted in ventricular hypertrophy similar to that observed in intact male sinoaortic denervated rats. Pretreatment with estradiol, however, suppressed the left ventricular hypertrophy in intact male rats but did not change the normal ventricular mass observed in intact female sinoaortic denervated rats. These results indicate that the development of left ventricular hypertrophy in sinoaortic denervated rats is modulated by sex hormones, and that testosterone exerts a facilitatory and estradiol an inhibitory action.