Adrenergic and reflex abnormalities in obesity-related hypertension.

Previous studies have shown that essential hypertension and obesity are both characterized by sympathetic activation coupled with a baroreflex impairment. The present study was aimed at determining the effects of the concomitant presence of the 2 above-mentioned conditions on sympathetic activity as well as on baroreflex cardiovascular control. In 14 normotensive lean subjects (aged 33. 5+/-2.2 years, body mass index 22.8+/-0.7 kg/m(2) [mean+/-SEM]), 16 normotensive obese subjects (body mass index 37.2+/-1.3 kg/m(2)), 13 lean hypertensive subjects (body mass index 24.0+/-0.8 kg/m(2)), and 16 obese hypertensive subjects (body mass index 37.5+/-1.3 kg/m(2)), all age-matched, we measured beat-to-beat arterial blood pressure (by Finapres device), heart rate (HR, by ECG), and postganglionic muscle sympathetic nerve activity (MSNA, by microneurography) at rest and during baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Blood pressure values were higher in lean hypertensive and obese hypertensive subjects than in normotensive lean and obese subjects. MSNA was significantly (P:<0.01) greater in obese normotensive subjects (49.1+/-3.0 bursts per 100 heart beats) and in lean hypertensive subjects (44.5+/-3.3 bursts per 100 heart beats) than in lean normotensive control subjects (32.2+/-2.5 bursts per 100 heart beats); a further increase was detectable in individuals with the concomitant presence of obesity and hypertension (62.1+/-3. 4 bursts per 100 heart beats). Furthermore, whereas in lean hypertensive subjects, only baroreflex control of HR was impaired, in obese normotensive subjects, both HR and MSNA baroreflex changes were attenuated, with a further attenuation being observed in obese hypertensive patients. Thus, the association between obesity and hypertension triggers a sympathetic activation and an impairment in baroreflex cardiovascular control that are greater in magnitude than those found in either of the above-mentioned abnormal conditions alone.

Early effects of total paracentesis and albumin infusion on muscle sympathetic nerve activity in cirrhotic patients with tense ascites.

BACKGROUND/AIMS: Cirrhotic patients with ascites are characterized by a marked activation of the sympathetic and the renin-angiotensin-aldosterone system. Total paracentesis is associated with a short-lived suppression of the renin-angiotensin-aldosterone system. Little information exists as to whether this favourable effect is parallelled by sympathoinhibition. METHODS: In 16 Child C cirrhotic patients (age: 57.1+/-6.2 years, mean+/-SEM) with tense ascites we assessed the time course of the effects of total paracentesis followed by intravenous albumin (6-8 g/l of ascites) on beat-to-beat mean arterial pressure (Finapres), heart rate, plasma norepinephrine, epinephrine (high performance liquid chromatography) and muscle sympathetic nerve activity (microneurography, peroneal nerve). Measurements were obtained under baseline conditions, during staged removal of ascitic fluid (250 ml/min) and 24 h later. The patient remained supine throughout the study period. RESULTS: Total paracentesis (10.6+/-1.3 l) induced a decrease in mean arterial pressure (from 95.0+/-2.6 mmHg to 88.2+/-3.2 mmHg, p<0.01), in heart rate (from 82.5+/-3.3 beats/min to 77.1+/-2.8 beats/min, p<0.01) and a reduction in plasma norepinephrine values (from 782+/-133 pg/ml to 624+/-103 pg/ml, p<0.01), which were substantially maintained 24 h later. In eight patients muscle sympathetic nerve activity did not change during paracentesis (from 65+/-7.1 bursts/min to 65+/-7.4 bursts/min, p=NS), but a marked reduction was observed 24 h later (48.4+/-5.6 bursts/min, p<0.01). CONCLUSIONS: These data provide the first evidence that total paracentesis exerts an acute marked sympathoinhibitory effect. Whether this is a long-lasting phenomenon and to what extent plasma expansion with albumin contributes to this effects need to be further addressed.

Effect of chronic angiotensin converting enzyme inhibition on sympathetic nerve traffic and baroreflex control of the circulation in essential hypertension.

BACKGROUND: Human studies have shown that the blood pressure lowering effects of angiotensin converting enzyme inhibitors are accompanied by a reduction in plasma norepinephrine levels. Whether this is due to central or peripheral mechanisms is unknown, however. OBJECTIVE: To evaluate the effects of chronic interference with the renin-angiotensin system on sympathetic nerve traffic and baroreflex control of vagal and adrenergic cardiovascular drive. PATIENTS AND METHODS: In 18 untreated mild to moderate essential hypertensive patients aged 48.5+/-1.9 years (mean+/-SEM), we measured mean arterial pressure (Finapres), heart rate (electrocardiogram), plasma renin activity (radioimmunoassay), plasma norepinephrine (high-performance liquid chromatography) and postganglionic muscle sympathetic nerve activity (microneurography at a peroneal nerve). In nine patients, measurements were performed before and after 2 months of oral administration of lisinopril (10 mg/day), while in the remaining nine patients they were performed before and after a 2 month observation period, without the drug administration. Measurements were performed at rest and during baroreflex stimulation and deactivation elicited by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. RESULTS: Lisinopril induced a marked increase in plasma renin activity (from 1.1+/-0.2 to 6.4+/-1.3 ng/ml per h, P< 0.01) and a reduction in mean arterial pressure (from 109.6+/-3.1 to 98.7+/-2.9 mmHg, P < 0.01) without affecting the heart rate. Plasma norepinephrine and muscle sympathetic nerve activity values were not significantly different before and after lisinopril treatment (plasma norepinephrine values changed from 290.4+/-39.2 to 308.1+/-67.1 pg/ml; muscle sympathetic nerve activity changed from 56.4+/-5.3 to 50.6+/-6.6 bursts/100 heart beats). Neither the sympathoinhibitory nor the sympathoexcitatory responses to phenylephrine and nitroprusside were affected by lisinopril, nor the concomitant bradycardia and tachycardia. The curves relating mean arterial pressure to heart rate and muscle sympathetic nerve activity values during baroreceptor manipulation were shifted to the left, indicating a resetting of the baroreflex to the lower blood pressure values achieved during treatment. CONCLUSIONS In essential hypertension, sympathetic nerve traffic is not affected by chronic angiotensin converting enzyme inhibitor treatment that effectively interferes with the renin-angiotensin system and lowers the elevated blood pressure. The baroreflex ability to modulate heart rate and central sympathetic outflow is also unaffected. These data argue against the existence of a central sympathoexcitatory effect of angiotensin II in this condition. They also indicate that antihypertensive treatment with an angiotensin converting enzyme inhibitor preserves autonomic reflex control, with favorable consequences for cardiovascular homeostasis.

Evidence of functional and structural cardiac abnormalities in cirrhotic patients with and without ascites.

Cirrhosis is associated with cardiovascular abnormalities. Scanty information is available as to whether these include left ventricle diastolic dysfunction and wall thickness increase. To this aim in 27 cirrhotic patients with tense ascites, 17 cirrhotic patients with previous episodes of ascites (not actual), and 11 controls we investigated by echocardiography and echocolor Doppler left ventricle diastolic function (E wave, A wave, E/A ratio, deceleration time of E wave), systolic function (ejection fraction), and wall thickness (left ventricle posterior wall thickness + interventricular septum thickness) along with neurohumoral variables. All measurements (supine position) were repeated after total paracentesis (10.7 +/- 0.6 L of ascites) in ascitic patients. Both in patients with and without ascites E/A ratio was reduced as compared with controls (0.93 +/- 0.07 and 0.97 +/- 0.06 vs. 1.18 +/- 0.08, P < .05) while left ventricle wall thickness was increased (18.6 +/- 0.6 and 20.1 +/- 0.8 vs. 17.2 +/- 0.7, P < .05 and P < .01, respectively), irrespective of the postviral or alcoholic cause of liver disease. In all cirrhotics both right and left atrial and right ventricle diameters were significantly greater. Ejection fraction was slightly but significantly (P < .01) reduced in ascitic patients. Paracentesis induced a reduction of the highly increased basal plasma renin activity, aldosterone, norepinephrine (P < .01), and epinephrine (P < .05) and improved diastolic function (E/A, P < .05). Systolic function was unaffected. Thus, irrespective of ascites and cause, advanced cirrhosis is associated with left ventricle diastolic dysfunction and wall thickness increase. We can speculate that neurohumoral overactivity, known to stimulate cardiac tissue growth, may challenge the heart, promoting fibrosis and exerting a further hindrance to ventricular relaxation in patients with cirrhosis experiencing episodes of ascites.

Effects of erythropoietin administration on blood pressure and urinary albumin excretion in rats.

The effects of recombinant human erythropoietin (rHuEPO) administration on blood pressure and urinary albumin excretion were studied in normotensive Wistar-Kyoto rats (WKY), in spontaneously hypertensive rats (SHR), and in SHR rats treated with an angiotensin converting enzyme inhibitor (SHR-ACEi). Rats were housed in metabolic cages and treated with rHuEPO (150 U/kg body weight [bw] three times a week) for 6 weeks. Control animals received the vehicle only (0.25 mL of physiological saline). An angiotensin converting enzyme inhibitor was administered in the drinking water for 6 weeks (spirapril 5 mg/kg bw). Systolic blood pressure (SBP), and 24 h urinary albumin excretion (UAE) were measured once a week. No significant differences in SBP were observed between rHuEPO and vehicle-treated normotensive animals at the end of the treatment (171.9 +/- 4.9 v 172.1 +/- 5.6 mm Hg, respectively). After 6 weeks, SBP was significantly higher in SHR and SHR-ACEi groups treated with rHuEPO than in control groups (239.8 +/- 7.3 and 243.0 +/- 7.3 mm Hg v 218.1 +/- 6.0 and 187.9 +/- 4.6 mm Hg, respectively); UAE was significantly higher in groups treated with rHuEPO than in control groups (WKY: 265.9 +/- 19.5 v 127.0 +/- 12.3 microg/100 g bw, SHR: 1668.4 +/- 564.6 v 234.8 +/- 22.9 microg/100 g bw, and SHR-ACEi: 1522.7 +/- 448.3 v 143.0 +/- 18.9 microg/100 g bw, respectively). We concluded that erythropoietin treatment causes an increase in arterial pressure in SHR only, and an increase in UAE in both normotensive and hypertensive rats. The albuminuric effect was not entirely dependent on increased blood pressure. The treatment with an angiotensin converting enzyme inhibitor did not modify either the proteinuric or the pressor effects.

Sympathetic activation and loss of reflex sympathetic control in mild congestive heart failure.

BACKGROUND: Baroreflex control of sympathetic activity is impaired in severe congestive heart failure (CHF), probably causing the marked sympathetic activation typical of this condition. Little information exists, however, as to whether baroreflex impairment and related sympathetic activation also occur in mild CHF. METHODS AND RESULTS: We studied 19 patients (age, 57.5 +/- 2.2 years, mean +/- SEM) with CHF in New York Heart Association (NYHA) class III or IV and with a marked reduction in left ventricular ejection fraction (LVEF, 30.1 +/- 1.5% from echocardiography) and 17 age-matched patients with CHF in NYHA class I or II and with an only slightly reduced LVEF (44.9 +/- 3.3%) that never was < 40%. Seventeen age-matched healthy subjects served as control subjects. Primary measurements included beat-to-beat arterial blood pressure (with the Finapres technique), heart rate (from ECG), and postganglionic muscle sympathetic nerve activity (MSNA, from microneurography at the peroneal nerve). Measurements were performed at baseline and during baroreceptor stimulation (intravenous phenylephrine infusion), baroreceptor deactivation (intravenous nitroprusside infusion), and cold-pressor test. Baseline blood pressure was similar in the three groups, whereas heart rate was progressively greater from control subjects to patients with mild and severe CHF, MSNA (bursts per 100 heart beats) increased significantly and markedly from control subjects to patients with mild and severe CHF (47.1 +/- 2.9 versus 64.4 +/- 6.2 and 82.1 +/- 3.4, P < .05 and P < .01, respectively). Heart rate and MSNA were progressively reduced by phenylephrine infusion and progressively increased by nitroprusside infusion. Compared with control subjects, the responses were strikingly impaired in severe CHF patients, but a marked impairment also was seen in mild CHF patients. On average, baroreflex sensitivity in mild CHF patients was reduced by 59.1 +/- 5.5% (MSNA) and 64.8 +/- 4.8% (heart rate). In contrast, reflex responses to the cold-pressor test were similar in the three groups. CONCLUSIONS: These results demonstrate that in mild CHF patients the baroreceptor inhibitor influence on heart rate and MSNA is already markedly impaired. This impairment may be responsible for the early sympathetic activation that occurs in the course of CHF.

Sympathetic activation in obese normotensive subjects.

Human obesity is characterized by profound alterations in the hemodynamic and metabolic states. Whether these alterations involve sympathetic drive is controversial. In 10 young obese subjects (body mass index, 40.5 +/- 1.2 kg/m2, mean +/- SEM) with normal blood pressure and 8 age-matched lean normotensive control subjects, we measured beat-to-beat arterial blood pressure (Finapres technique), heart rate (electrocardiogram), postganglionic muscle sympathetic nerve activity (microneurography at the peroneal nerve), and venous plasma norepinephrine (high-performance liquid chromatography). The measurements were performed in baseline conditions and, with the exception of plasma norepinephrine, during baroreceptor stimulation and deactivation caused by increases and reductions of blood pressure via intravenous infusions of phenylephrine and nitroprusside. Baseline blood pressure and heart rate were similar in obese and control subjects. Plasma norepinephrine was also similar in the two groups. Muscle sympathetic nerve activity, however, was 38.6 +/- 5.1 bursts per minute in obese subjects and less than half that level in control subjects (18.7 +/- 1.3 bursts per minute), the difference being highly statistically significant (P < .02). Muscle sympathetic nerve activity and heart rate were reduced during phenylephrine infusion and increased during nitroprusside infusion, but the changes were about half as great in obese subjects as in control subjects. Thus, even in the absence of any blood pressure alteration, human obesity is characterized by a marked sympathetic activation, possibly because of an impairment of reflex sympathetic restraint. This may be involved in the high rate of hypertension and cardiovascular complications seen in obesity.

Neural mechanisms in hypertension and the elderly.

Experimental animal studies carried out over the past 40 years have unequivocally shown that neurogenic mechanisms are involved in the pathogenesis of hypertension. The results of these studies also suggest that neural factors are important not only in the development but also in the maintenance of the high blood pressure condition. Whether this is the case also for human hypertension has been matter of debate for several decades. However, recent studies in man by employing sophisticated techniques for assessing sympathetic tone, i.e. the norepinephrine radiolabelled technique and microneurographic recording of sympathetic nerve traffic, support the hypothesis that alterations in sympathetic modulation of the cardiovascular system take place in hypertension and may have a pathogenetic relevance in age-related blood pressure increase.

Mechanisms responsible for sympathetic activation by cigarette smoking in humans.

BACKGROUND: The pressor and tachycardic effects of cigarette smoking are associated with an increase in plasma catecholamines, suggesting the dependence of these effects on adrenergic stimulation. Whether the stimulation occurs at a central or a peripheral level and whether reflex mechanisms are involved is unknown. METHODS AND RESULTS: In nine normotensive healthy subjects (age, 33.0 +/- 3.5 years, mean +/- SEM), we measured blood pressure (Finapres device), heart rate (ECG), calf blood flow and vascular resistance (venous occlusion plethysmography), plasma norepinephrine and epinephrine (high-performance liquid chromatography assay), and postganglionic muscle sympathetic nerve activity (microneurography from the peroneal nerve) while subjects were smoking a filter cigarette (nicotine content, 1.1 mg) or were in control condition. Cigarette smoking (which raised plasma nicotine measured by high-performance liquid chromatography from 1.0 +/- 0.9 to 44.2 +/- 7.1 ng/mL) markedly and significantly increased mean arterial pressure (+13.2 +/- 2.3%), heart rate (+30.3 +/- 4.7%), calf vascular resistance (+12.1 +/- 4.9%), plasma norepinephrine (+34.8 +/- 7.0%), and plasma epinephrine (+90.5 +/- 39.0%). In contrast, muscle sympathetic nerve activity showed a marked reduction (integrated activity -31.8 +/- 5.1%, P < .01). The reduction was inversely related to the increase in mean arterial pressure (r = -.67, P < .05), but the slope of the relation was markedly less (-54.1 +/- 7.5%, P < .05) than that obtained by intravenous infusion of phenylephrine in absence of smoking. The hemodynamic and neurohumoral changes were still visible 30 minutes after smoking and occurred again on smoking a second cigarette. Sham smoking was devoid of any hemodynamic and neurohumoral effect. CONCLUSIONS: These data support the hypothesis that in humans the sympathetic activation induced by smoking depends on an increased release and/or a reduced clearance of catecholamines at the neuroeffector junctions. Central sympathetic activity is inhibited by smoking, presumably via a baroreceptor stimulation triggered by the smoking-related pressor response. The baroreflex is impaired by smoking, however, indicating that partial inability to reflexly counteract the effect of sympathetic activation is also responsible for the pressor response.

Effect of octreotide on catecholamine plasma levels in patients with chromaffin cell tumors.

Many chromaffin cell tumors contain somatostatin (SS), and most of them are receptor-positive by in vitro autoradiography and by in vivo administration of radiolabeled SS analogs. We evaluated the effect of a 2-hour infusion of 50 micrograms octreotide on plasma norepinephrine (NE) and epinephrine (E) levels in 6 patients with chromaffin cell tumors. To ascertain the biological activity of octreotide, plasma insulin levels were also measured. Infusion of octreotide was followed in all the patients but 1 by a progressive decrease of plasma NE levels. On the average, plasma NE decreased significantly during octreotide administration, halving its baseline levels at the end of the infusion (51.3 +/- 11.46%, p < 0.05) and rising again slowly thereafter. A slight reduction of plasma E levels was also recorded at the end of octreotide infusion (76.1 +/- 13.77% of baseline, NS) with a prompt return of hormone concentrations to preinfusion values. During octreotide administration, plasma insulin displayed an early and steep fall (49.7 +/- 4.61% of baseline, p < 0.03, at 60 min) with a tendency to escape from inhibition before termination of the infusion. In 5/6 patients, 2 of whom were normotensive before the study and 1 the day of the test, blood pressure did not change during octreotide infusion. In the other patient, blood pressure fell from baseline values of 160/100 to 120/70 mm Hg at 120 min and rebounded to 205/100 mm Hg at 240 min. In conclusion, the short-term administration of low-dose octreotide is capable of lowering NE levels, though with no consistent effect on blood pressure, in patients with chromaffin cell tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Physical exercise in essential hypertension.

Although several studies have shown that physical training lowers blood pressure values both in normotensives and in hypertensives, the mechanisms accounted for this effect are not clearly elucidated. It has been reported that the decrease in blood pressure and heart rate that accompanies physical training is associated not only with an increase in vagal tone but also with a reduction in plasma norepinephrine levels. Whether this reduction really means a decrease in sympathetic neural discharge is unknown, however. To clarify this issue, we have performed in 7 normotensives direct recording of postganglionic muscle sympathetic nerve activity from the peroneal nerve by microneurography before and after 10 weeks of an endurance training which increased oxygen consumption by 10%. It was shown that the blood pressure lowering effect of the training program was accompanied by a marked reduction in resting sympathetic nerve activity. These data provide the first direct evidence that in man, the blood pressure reduction induced by physical training is mediated by the neural sympathetic mechanisms.

Effect of detraining on the cardiopulmonary reflex in professional runners and hammer throwers.

In professional athletes with marked cardiac hypertrophy, reflex influences originating from cardiopulmonary receptors are impaired. To determine whether the reflex is restored after termination of physical training and regression of cardiac hypertrophy 8 former athletes (age 31 +/- 6 years, mean +/- SD) who stopped agonistic activity for 5 +/- 1 years were compared with 15 sedentary subjects (27 +/- 7 years) and 19 active professional athletes (22 +/- 7 years). Cardiopulmonary receptor stimulation and deactivation were obtained by increasing and reducing left ventricular end-diastolic diameter (echocardiography) through leg raising and nonhypotensive lower body negative pressure, respectively. Left ventricular mass index (echocardiography) was markedly and significantly (p less than 0.01) greater in athletes (135 +/- 6 g/m2) than in former athletes (105 +/- 4 g/m2) whose value was similar to that of sedentary subjects (98 +/- 4 g/m2). The reduction in forearm vascular resistance and plasma norepinephrine induced by increasing left ventricular end-diastolic diameter was 24 and 23% less in athletes than in former athletes whose responses were similar to those of sedentary subjects. This was the case also for the responses induced by reducing left ventricular end-diastolic diameter. In contrast, the hemodynamic responses to cold pressor test were similar in the 3 groups. It is concluded that the impairment of the cardiopulmonary reflex observed in athletes is largely reversible when physical training is terminated. This may be due to regression of left ventricular hypertrophy.

Cardiopulmonary receptor reflexes in normotensive athletes with cardiac hypertrophy.

Cardiopulmonary receptor control of the circulation is impaired in a variety of diseases having cardiac hypertrophy as a common feature. Whether this also occurs in the so-called "physiological" cardiac hypertrophy of the athlete, however, is unknown. We studied nine sedentary healthy subjects and 19 age-matched professional runners or hammer throwers who had trained at least 2 hours per day, 5 days per week for 7 years. The left ventricular mass index (echocardiography) was 99 +/- 7.4 and 135 +/- 5.9 g/m2 in the two groups, respectively. Cardiopulmonary receptor stimulation and deactivation were obtained by increasing and reducing left ventricular end-diastolic diameter for 5 minutes by leg raising and lower body negative pressure, keeping both stimuli at a level not affecting blood pressure and heart rate. In the sedentary healthy subjects, forearm vascular resistance (the ratio between mean arterial pressure and forearm blood flow) and plasma norepinephrine fell during leg raising (forearm vascular resistance, -7 +/- 1.7 units; norepinephrine, -57.4 +/- 1.4 pg/ml) and increased during lower, body negative pressure (forearm vascular resistance, 20 +/- 5.3 units; norepinephrine, 97.7 +/- 21.5 pg/ml). For similar or greater alterations in left ventricular end-diastolic diameter, the correspondent changes observed in the professional runners or hammer throwers were -5.3 +/- 1.3 units (forearm vascular resistance), -35.4 +/- 9.6 pg/ml (norepinephrine), 9.1 +/- 1.4 units (forearm vascular resistance), and 30.9 +/- 6.9 pg/ml (norepinephrine). This represented an attenuation of 25%, 38%, 55%, and 68%, respectively (p less than 0.01), of the control response.(ABSTRACT TRUNCATED AT 250 WORDS)

Nicorandil, a new vasodilator drug, in patients with essential hypertension.

In 12 mild to moderate hypertensive patients we investigated the acute antihypertensive efficacy of three different doses of nicorandil, a new vasodilating agent which probably acts by increasing the potassium efflux from smooth muscle cells and causing a cellular hyperpolarization. After a 3-day placebo period the patients were given, according to a double-blind Latin-square randomized design, 10, 20 and 30 mg nicorandil as a single acute dose every other day. Blood pressure and the heart rate were measured in both supine and upright positions at various times for 24 h after the dosing; fractional urine collections were obtained at the end of the placebo period and after each active dose. All doses of nicorandil similarly and significantly (P less than 0.01) reduced supine blood pressure, with a peak after 4-6 h (10 mg: -21/-8 mmHg; 20 mg: -20/-9 mmHg; 30 mg: -29/-17 mmHg), and the effect was still present, though reduced, after 24 h; no change in the heart rate was observed. The results from the upright position were similar. There were no significant changes in urine volume and electrolyte excretion during the nicorandil administration. The three different doses of nicorandil caused similar acute blood pressure reductions without change in the heart rate, nor in the urine volume and urinary sodium.

Nadolol prevents the exercise-induced rise in lymphocyte beta-receptor number in borderline hypertension.

Thirteen borderline hypertensives were investigated at rest and during dynamic exercise, before and after therapy with nadolol (40-80 mg/day for 7-28 days), in order to evaluate regulation of the number of lymphocyte beta-receptors. Systolic blood pressure and the heart rate were measured before and after 15 min of bicycle exercise, both with and without nadolol therapy; blood samples were withdrawn for adrenaline, noradrenaline and lymphocyte beta-receptor determinations. Nadolol induced a significant decrease in systolic blood pressure and the heart rate at rest, while plasma catecholamines and lymphocyte beta-receptors did not change significantly. Of the physiological responses to dynamic exercise (increases in systolic blood pressure, heart rate, plasma noradrenaline levels and adrenaline and lymphocyte beta-receptors), only the rise in beta-receptors was entirely prevented, and the increase in the heart rate was significantly attenuated by nadolol. It is suggested that the lack of a rise in the number of beta-receptors during exercise may contribute to the blunted exercise-induced tachycardia in patients taking nadolol.

Cardiopulmonary reflex before and after regression of left ventricular hypertrophy in essential hypertension.

Studies that have examined the cardiopulmonary receptor control of circulation in hypertension have produced conflicting results. In 10 normotensive subjects and in age-matched essential hypertensive subjects without (n = 10) or with left ventricular hypertrophy (n = 12), as well as in seven subjects of the latter group restudied after 1 year of treatment that induced regression of cardiac hypertrophy, we examined the cardiopulmonary reflex by increasing central venous pressure and stimulating cardiopulmonary receptors through passive leg raising and by reducing central venous pressure and deactivating cardiopulmonary receptors through nonhypotensive lower body negative pressure. Reflex responses were measured as changes in forearm vascular resistance (mean blood pressure divided by plethysmographically measured blood flow), plasma norepinephrine concentration, and plasma renin activity. In hypertensive subjects without left ventricular hypertrophy, stimulation and deactivation of cardiopulmonary receptors caused changes in forearm vascular resistance, norepinephrine concentration, and plasma renin activity that were modestly reduced as compared with those in normotensive subjects. However, all these changes were markedly reduced in hypertensive subjects with left ventricular hypertrophy. Following regression of left ventricular hypertrophy, the changes in vascular resistance, plasma norepinephrine, and plasma renin activity induced by cardiopulmonary receptor manipulation all improved markedly. These results demonstrate that cardiopulmonary receptor regulation of peripheral vascular resistance and of neurohumoral variables is impaired in essential hypertension and that the impairment is much more pronounced when this condition is associated with cardiac structural alterations. Therapeutic regression of these alterations, however, leads to a marked improvement of this reflex, with consequent favorable effects on circulatory homeostasis.

Cardiopulmonary receptor regulation of renin release.

Cardiopulmonary receptors have been shown to modulate renin release in animals. However, their involvement in reflex control of renin in humans has never been unequivocally established. This report reviews data on the effects on plasma renin activity of maneuvers (lower body negative pressure and passive leg raising) that reduce and increase central venous pressure and cardiac diameter without affecting blood pressure and heart rate, thereby deactivating and stimulating cardiopulmonary receptors with little or no involvement of the arterial baroreceptors. In normotensive subjects, reduction in central venous pressure was accompanied by an increase in plasma renin activity that was similar to the increase observed during tilt that reduced central venous pressure to a similar extent. Conversely, an increase in central venous pressure was accompanied by a reduction in plasma renin activity. The increase in plasma renin activity that followed the reduction in central venous pressure was drastically attenuated in four patients who had undergone cardiac transplantation, along with other reflex effects (changes in forearm vascular resistance and plasma norepinephrine) of cardiopulmonary receptor manipulations. There was a modest reduction in the overall reflex changes in plasma renin activity in patients with mild to moderate essential hypertension compared with normotensive subjects. However, patients with essential hypertension and cardiac hypertrophy showed marked attenuation of all reflex influences of the cardiopulmonary receptors. In five subjects, therapeutic regression of this structural alteration was associated with a clear improvement in the cardiopulmonary reflex. Thus, in humans, cardiopulmonary receptors exert an important reflex control of renin release. This control (which is due in part to receptors located in the cardiac walls) is moderately affected by a mild to moderate blood pressure elevation but is markedly impaired when the elevation produces structural alterations in the heart. Preliminary evidence, however, suggests that the cardiopulmonary reflex may be improved by a reduction in cardiac hypertrophy.