Modulation of sympathetic coronary vasoconstriction by cardiac renin-angiotensin system in human coronary heart disease.

BACKGROUND: In humans, angiotensin II enhances the sympathetic coronary vasoconstriction elicited by the cold pressor test (CPT) and diving. Whether this enhancement depends on the circulating angiotensin II or on the locally produced angiotensin II is unknown, however. METHODS AND RESULTS: We addressed this issue in 14 patients with severe coronary artery disease by evaluating the effects of a 2-minute CPT (n=14) and a 30-second dive (n=8) on mean arterial pressure (MAP, arterial catheter), heart rate (ECG), coronary sinus blood flow (CBF, thermodilution technique), and coronary vascular resistance (MAP/CBF ratio). The 2 stimuli were applied at the end of left intracoronary infusion of either saline or benazeprilat diluted at the concentration of 25 microgram/mL. The rate of benazeprilat infusion had been preliminarily demonstrated to reduce angiotensin II concentration in the coronary sinus without affecting its arterial concentration. The changes in MAP and heart rate induced by CPT and diving were superimposable during saline and benazeprilat infusions. The decrease in CBF induced by CPT and diving during saline infusion was changed into an increase during benazeprilat infusion with a significant attenuation of the coronary vasoconstrictor response. CONCLUSIONS: In patients with coronary artery disease, an attenuation of sympathetic coronary vasoconstriction can be obtained by reducing cardiac angiotensin II formation without involving circulating angiotensin II. This suggests a role of the tissue renin-angiotensin system in modulating autonomic cardiac drive in humans.

Baroreflex and non-baroreflex modulation of vagal cardiac control after myocardial infarction.

Vagal control of sinus node exerted by arterial baroreceptors is markedly impaired 48 hours after acute myocardial infarction (AMI), but it recovers 10 days later. However, it is unknown whether this recovery is peculiar to baroreceptor vagal control or reflects normalization of the overall vagal modulation of heart rate. In 21 untreated patients (aged 51+/-3 years, mean +/- SEM) studied 10+/-1 and 21+/-1 days after an AMI and in 13 healthy controls (aged 47+/-2 years), we examined the increases in RR interval (electrocardiogram) induced by carotid baroreceptor stimulation via a neck chamber and by immersion of the face in iced water for 15 seconds (diving reflex). Both 10 and 21 days after AMI, baseline blood pressure and RR interval values were superimposable to those obtained in controls. Ten days after AMI, the bradycardic responses to carotid baroreceptor stimulation were similar to those seen in controls (maximal RR interval lengthenings: 248+/-34 vs 270+/-31 ms, respectively, p = NS) and remained virtually unchanged later. In contrast, the bradycardic response to diving was reduced in patients after AMI compared with controls (maximal RR interval lengthenings: 203+/-43 vs 325+/-52 ms, respectively, p <0.05) and did not improve later. Thus, in AMI recovery of the early impairment of baroreceptor-heart rate control does not reflect normalization of vagal cardiac control, which remains lower than normal values at a time when the baroreflex is restored.

An improved method for coronary sinus blood flow monitoring by intravascular Doppler technique.

In order to obtain accurate measurements of coronary sinus blood flow (CSBF), a new catheter (7 French) with a radiopaque, flexible, and basket-shaped tip was developed for guiding a standard 3 Fr Doppler catheter in the coronary sinus (CS) in man. The radiopaque "basket" tip of the catheter allows the operator to stabilize the position of the Doppler transducer in the center of the CS and to accurately measure the CS internal diameter radiologically. CSBF was calculated as the product of CS cross-sectional area by mean CSBF velocity. Doppler-derived CSBF values at rest and during handgrip were compared with those obtained by the local thermodilution technique in 16 patients undergoing diagnostic coronary angiography. During handgrip, mean CSBF increased from 154+/-23 (rest) to 299+/-34 mL/min by the Doppler method and from 148+/-22 to 288+/-32 mL/min by the thermodilution technique. A good correlation (r = 0.86) between the CSBF values with the two techniques was observed. The authors conclude that the intravascular Doppler technique associated with the use of the basket guide catheter provides an accurate and simple tool for monitoring CSBF in patients.

Intracoronary angiotensin II potentiates coronary sympathetic vasoconstriction in humans.

BACKGROUND: In humans with coronary artery disease, ACE inhibition attenuates coronary sympathetic vasoconstriction. Whether this is due to removal of angiotensin (Ang) II production or to a reduced bradykinin breakdown, however, is unknown. METHODS AND RESULTS: In eight normotensive patients with angiographic evidence of mild left coronary artery lesions (< or = 50%), mean arterial pressure (MAP, intra-arterial catheter), heart rate (HR, ECG lead), coronary sinus blood flow (CBF, thermodilution method), and coronary vascular resistance (CVR, ratio between MAP and CBF) were measured before and during a 15-minute left intracoronary infusion of Ang II at a dose that had no direct coronary or systemic vasomotor effects. The same measurements were made before and during a 15-minute infusion of saline. A 2-minute cold pressor test (CPT) and a 45-second diving were performed at the end of either infusion period. These maneuvers were used because their coronary vasomotor effects are abolished by phentolamine and thus depend on sympathetic activation. During saline infusion, both CPT and diving caused a marked increase in MAP. HR increased with CPT and fell with diving. CBF increased in parallel to the MAP increase, with little change in CVR. The MAP and HR responses were similar during Ang II infusion, which, however, caused either no change or a reduction in CBF with a consequent marked increase in CVR with both CPT and diving. In four additional patients, the diameter of the stenotic vessels remained unchanged during the CPT performed under saline and Ang II infusion. CONCLUSIONS: Ang II markedly enhances sympathetic influences on coronary circulation in humans, presumably by acting at the arteriolar level. This may explain the blunting effect of ACE inhibition on sympathetic coronary vasoconstriction in patients with coronary artery disease.

Nimodipine as a modulator of resistance to doxorubicin in human colon-adenocarcinoma cells.

The potential of the dihydropyridine nimodipine (NIMO), a drug currently used for cerebrovascular disorders, in modulating the cytotoxicity of doxorubicin (DX) was investigated, in comparison to verapamil (VER), in human colon adenocarcinoma cell lines sensitive (LoVo) or resistant (LoVo/DX) to anthracycline. NIMO selectively enhanced DX activity in the resistant cell line. In particular, the DX concentration able to inhibit cell growth by 50% was reduced by 2.6 to 5.7-fold as a function of the time of exposure to the modulator. The increase in DX accumulation in LoVo/DX nuclei after exposure to NIMO was about 4-fold that observed in the nuclei of resistant cells exposed to DX alone. Similar results were obtained in LoVo/DX cells following treatment with equimolar concentrations of VER. Again, both NIMO and VER failed to interfere with the immunoreactivity of LoVo/DX cells to the MRK16 monoclonal antibody. NIMO did not inhibit H-3-azidopine binding to LoVo/DX cells, but, unlike VER, it caused a selective hyperpolarization of the cell membrane in resistant cells.

Effects of amlodipine on coronary hemodynamics and vascular responses to sympathetic stimulation in patients with coronary heart disease.

Dihydropyridines (DHPs) exert a powerful coronary vasodilator action, but whether they actually affect the coronary vasomotor effects elicited by an increase in cardiac sympathetic drive is controversial. We assessed the effects of the DHP calcium antagonist amlodipine on coronary hemodynamics and vascular response to sympathetic activation in patients with coronary heart disease. In the control condition, mean arterial pressure (MAP, aortic catheter), heart rate (HR, ECG), rate-pressure product (RPP), coronary sinus blood flow (CBF, thermodilution) and coronary vascular resistance (CVR) (ratio between MAP and CBF) were measured in all our case series (13 patients with angiographically documented severe coronary artery disease) before and during a 2-min cold pressor test (CPT) and a 30-s diving (D) and, in the 8 patients of this case series who were smokers, also before and during smoking a cigarette (S, nicotine content 1.0 mg for 10 min). The same protocol used in control condition was repeated 30 min after intravenous (i.v.) bolus administration of 11 mg amlodipine. CPT, diving, and smoking increased MAP and RPP and caused a marked and significant increase in CVR (+12.1 +/- 4.8, +30.4 +/- 6.8, and +16.8 +/- 7.2%, respectively). Amlodipine reduced MAP, increased CBF, and caused a marked decrease in CBF. The drug did not modify responses to CPT and diving or pressure and HR responses to smoking, whereas the smoking-induced increase in coronary vascular resistance was attenuated after amlodipine administration (+3.2 +/- 2.7%, p < 0.05 vs. control condition). Thus, amlodipine does not attenuate the sympathetic coronary vasoconstrictor effects of CPT and diving.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary vascular reactivity and calcium antagonist therapy in patients with angina.

In patients with severe coronary atherosclerotic disease, the angiotensin-converting enzyme inhibitor captopril attenuates the vasoconstriction induced by the cold pressor test and diving (two stimuli that cause reflex sympathetic activation) via removal of the facilitating effect of angiotensin II on sympathetic drive. However, whether calcium antagonists also have this effect is not clear. We evaluated the effects of a single 11-mg intravenous dose of the dihydropyridine calcium antagonist amlodipine on the coronary vascular response to the cold pressor test, a 30-s application of the dive reflex and cigarette smoking (whose effects on the coronary circulation also involve the sympathetic nervous system). In 13 normotensive male patients with severe stenoses of the left anterior descending coronary artery, the cold pressor test and diving reflex increased mean arterial pressure and rate-pressure product and caused a marked and significant rise in coronary vascular resistance (+ 12.1 +/- 4.8% and +30.4 +/- 6.8%, respectively). Mean arterial pressure, rate-pressure product, and coronary vascular resistance also increased markedly during smoking. Amlodipine caused a reduction in baseline mean arterial pressure, an increase in baseline coronary blood flow, and a marked fall in baseline coronary vascular resistance (-19.2 +/- 3.1%; p < 0.01). The coronary vascular responses to the cold pressor test and the diving reflex were unchanged with amlodipine. However, the smoking-induced increase in coronary vascular resistance was significantly attenuated after amlodipine (+3.2 +/- 2.7% vs. +16.8 +/- 7.2%; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Impairment of the arterial baroreflex during symptomatic and silent myocardial ischemia in humans.

OBJECTIVES: The aim of this study was to assess whether transient episodes of symptomatic or silent myocardial ischemia after baroreceptor modulation of heart rate. BACKGROUND: Animal and human studies have shown that myocardial infarction is accompanied by an impairment of the baroreceptor influences on the sinus node. However, whether this also occurs during transient myocardial ischemia has never been documented. METHODS: In 12 patients undergoing coronary angiography, systolic blood pressure (intraarterial catheter) was reduced by an intravenous bolus of nitroglycerin during a spontaneous episode of transient chest pain and myocardial ischemia (ST segment depression on the electrocardiogram) and 30 min after recovery. The slope of the linear regression between the decrease in systolic blood pressure and the RR interval shortening was taken as the measure of baroreflex sensitivity. RESULTS: During ischemia, baroreflex sensitivity was 1.3 +/- 0.3 ms/mm Hg (mean +/- SEM), whereas after recovery it was markedly and significantly greater (2.6 +/- 0.5 ms/mm Hg, p < 0.01). Similar results were obtained in eight other patients who experienced a silent ischemic episode either spontaneously or during coronary angioplasty. The reduction in baroreflex sensitivity was similarly pronounced during inferior (10 patients) and anterior (10 patients) ischemia, and its magnitude showed little or no relation to the ischemia-dependent changes in blood pressure and heart rate. CONCLUSIONS: Transient myocardial ischemia is associated with marked baroreflex impairment. The impairment occurs even during symptomless ischemic episodes and is therefore not related to pain or to other nonspecific influences on the baroreflex.

RAA system and cardiovascular control in normal subjects, hypertensives and patients with congestive heart failure.

The involvement of the renin-angiotensin-aldosterone (RAA) system, particularly angiotensin II, in the pathogenesis of hypertension is widely acknowledged and is supported by several observations: the RAA system has been shown to be critically involved in the development of some experimental hypertensions; activation of the RAA system appears to be the crucial factor involved in the maintenance of the BP elevation in some antihypertensive patients; while drugs which interfere with the production of angiotensin II reduce BP in a large number of hypertensive patients. It is now clear that the chronic BP elevations caused by circulating (and perhaps locally produced) angiotension II may have adverse effects on organ function and protection: for example, induction of cardiac hypertrophy and vascular hypertrophy and/or hyperplasia, reduction of arterial compliance and reduction in vagal tone and facilitation of sympathetic activity on cardiac and vascular targets. At the cardiac level, the renin-angiotensin sympathetic interaction may enhance electrical instability, thereby favouring arrhythmias and increasing mortality after a myocardial infarction. It finally enhances coronary vasoconstriction in man, producing or favouring myocardial ischaemia.

Aprocta matronensis in crows (Corvus corone corone) from northern Italy.

Aprocta matronensis (Nematoda, Spirurida) has been found in the orbital cavities of carrion crows. Hooded crows and crows from the hybrid crow zone in the studied areas were not infected. The parasite population showed the typical morphology described for this species. This is the first record of A. matronensis in crows in Italy and in Corvus corone corone. Some hypotheses about the distribution of the parasites in crow populations are discussed.

[Noninvasive evaluation of cardiac index and ejection fraction in ischemic heart disease. Comparison of thoracic bioimpedance, thermodilution and cineventriculography]. / Valutazione non invasiva dell'indice cardiaco e della frazione di eiezione nella cardiopatia ischemica. Confronto tra bioimpedenza toracica, termodiluizione e cineventricolografia.

Aim of the study was to verify the reliability of thoracic bioimpedance cardiography (TEB) in detection, non-invasively, cardiac index (IC) and ejection fraction (FE), compared to simultaneous evaluation by invasive thermodilution (TD) in 39 patients with acute myocardial infarction in Killip class I-II (group I), and by cineventriculography (CVG) in 26 patients with chronic coronary artery disease in NYHA class I-II (group II). In order to define the reproducibility of TEB values, in the latter patients, the above mentioned parameters were evaluated 6 times more, running the first evaluation. The statistical analysis was performed by the linear regression test and the Student's "t" test and by the test of variance for the reproducibility evaluation. Results (mean +/- SD) were as follows: group I: TEB-IC 2.89 +/- 0.63; TD-IC 2.83 +/- 0.56 (1/min/m2); r = 0.68; p < 0.01. Group II: TEB-IC 2.88 +/- 0.71; CVG-IC 3.48 +/- 0.66; r = 0.77; p < 0.001; TEB-FE 57.7 +/- 6.8%; CVG-FE 58.1 +/- 13.7%; r = 0.40; p = ns. Results of the reproducibility referred to the 6 measurements (mean +/- SD) were the follows: TEB-IC (1/min/m2) (1) 2.83 +/- 0.76; (2) 2.85 +/- 0.73; (3) 2.8 +/- 0.79; (4) 2.83 +/- 0.71; (5) 2.87 +/- 0.81; (6) 2.88 +/- 0.8, p = ns, the variability was assesses within +/- 9.3%. TEB-FE (%): (1) 56.7 +/- 6.2; (2) 55.8 +/- 5; (3) 57.1 +/- 5.5; (4) 56.1 +/- 6.1; (5) 55.4 +/- 5.8; (6) 57.3 +/- 6.3, p = ns; the variability was assessed within +/- 9.1%. The analysis of the results showed a good correlation in the IC detection among TEB and the compared techniques, conversely TEB evaluation of FE appear of poor values in this kind of patients. Relatively to the results of the reproducibility this unquestionable characteristic of TEB was demonstrated.

ACE inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease.

BACKGROUND: In humans, angiotensin converting enzyme (ACE) inhibition attenuates the vasoconstriction induced by sympathetic stimulation in a number of peripheral districts. Whether this is also the case in the coronary circulation is unknown, however. METHODS AND RESULTS: In nine normotensive patients with angiographically assessed coronary atherosclerosis, we measured the changes in mean arterial pressure (intra-arterial catheter), heart rate, rate-pressure product (RPP), coronary sinus blood flow (CBF, thermodilution method), and coronary vascular resistance (CVR, ratio between mean arterial pressure and CBF) induced by the cold pressor test (CPT, 2 minutes) and diving (30 seconds), i.e., two stimuli eliciting a sympathetic coronary vasoconstriction. The measurements were performed in the control condition and 30 minutes after captopril 25 mg p.o. In the control condition, CPT caused an increase in mean arterial pressure and heart rate. Despite the increase in RPP (+20.7 +/- 3.2%, p less than 0.01), CBF did not change and CVR increased (+12.2 +/- 4.0%, p less than 0.05). diving caused an increase in mean arterial pressure and a reduction in heart rate. RPP increased (+14.3 +/- 3.5%, p less than 0.01), but despite this increase, there was a reduction in CBF and a marked increase in CVR (+37.3 +/- 7.4%, p less than 0.01). Captopril did not modify the blood pressure and heart rate responses to both stimuli except for a slight accentuation of the bradycardia to diving. Despite the unchanged or only slightly reduced RPP response, the increase in CVR was markedly and significantly attenuated (p less than 0.01). CONCLUSIONS: ACE inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease. This is probably due to removal of the facilitating influence of angiotensin II on sympathetic modulation of coronary vasomotor tone.

Coronary response to diving in subjects with mild and severe left coronary artery disease.

The cold pressor test (CPT) is commonly used to determine the vasospastic origin of angina and to investigate the factors modulating coronary vasomotor tone. However, coronary vasoconstriction associated with this manoeuvre is often limited, particularly in patients with mild coronary atherosclerosis. To identify stimuli that can more powerfully constrict the coronary arteries we compared the effects on coronary blood flow (thermodilution) and vascular resistance (mean aortic pressure divided by coronary blood flow) of CPT (2 min) and diving (D, 45 s) in subjects with angiographically documented mild (n = 11) or severe (n = 11) left anterior descending coronary artery stenosis. In subjects with severe coronary artery stenosis the rate-pressure product increased to a similar extent with CPT and D. The latter stimulus, however, caused a more marked fall in coronary blood flow and a much more pronounced increase in coronary resistance as compared to CPT (+44 +/- 3.1% vs +19 +/- 1.6%, P less than 0.01). In the face of a similar increase in rate-pressure product, D caused a significant increase in coronary vascular resistance also in patients with mild coronary artery stenosis (less than or equal to 50%) in which CPT failed to induce any coronary vasoconstriction (+16 +/- 1.8% vs +0.3 +/- 1.3%, P less than 0.01). Thus, diving is a much more powerful coronary vasoconstrictor stimulus than CPT. It can thus replace CPT when an increase in coronary resistance is needed for diagnostic purposes or for investigating abnormalities in coronary vascular regulation.

Use of intravenous digital subtraction ventriculography in the evaluation of left ventricle volumes and ejection fraction.

Although intravenous digital subtraction ventriculography (IDSV) is increasingly used to estimate end-diastolic left ventricular volume (EDV), end-systolic left ventricular volume (ESV) and left ventricular ejection fraction (EF), its ability to reproduce the precise estimates provided by left ventricle cineangiography (LVCA) and its role in clinical cardiology have not been unequivocally established. In 32 patients subjected to cardiac catheterization for a variety of cardiac disorders and a normal or reduced left ventricular function the EDV, ESV and EF provided by a 30 degrees right anterior oblique LVCA were compared with those provided by a 30 degrees right anterior oblique IDSV. The mean EDV, ESV and EF obtained by IDSV in the 32 patients were superimposable on those obtained by LVCA. The individual EDV, ESV and EF values provided by the two methods were all related in a close linear fashion. For EF the correlation coefficient was 0.98 and the 90% confidence interval of the mean difference between the two series of values was +/- 6.1%, i.e. +/- 10% error compared to the mean EF provided by LVCA. Thus IDSV is a reliable and not too invasive method for estimating left ventricle volumes and ejection fraction. It might provide serial estimations with a better assessment of the evolution of a patient's disease and the effect of treatment.

Haemodynamic effects of ACE inhibitors.

This paper reviews the haemodynamic effects of angiotensin-converting enzyme (ACE) inhibitors in hypertension, focusing on their ability to cause a fall in systemic vascular resistance, with no change in cardiac output and no reduction and even an increase in blood flow to vital organs such as the brain, the kidney and the heart. The haemodynamic effects of ACE inhibitors are qualitatively similar in congestive heart failure, except that, in the presence of impaired cardiac function, the fall in resistance is accompanied by a pronounced increase in cardiac output and tissue perfusion. In both conditions ACE inhibition opposes sympathetic influences and enhances vagal influences and, in hypertension, this intervention is followed by a regression of left ventricular hypertrophy providing a multifold background for a cardioprotective action. The new ACE inhibitor quinapril appears to share the haemodynamic effects of other ACE inhibitors with an improvement of cardiovascular function in congestive heart failure.

Effect of angiotensin converting enzyme inhibition on cardiovascular regulation during reflex sympathetic activation in sodium-replete patients with essential hypertension.

In order to investigate whether angiotensin II (Ang II) may contribute to cardiovascular regulation through facilitation of the adrenergic function, we examined the haemodynamic and humoral effects of the application of lower-body negative pressure (LBNP) in sodium-replete patients with essential hypertension before and after acute and chronic angiotensin converting enzyme (ACE) inhibition. We measured the changes in blood pressure, heart rate, central venous pressure, forearm blood flow, plasma noradrenaline, renin activity and Ang II induced by LBNP of two different magnitudes: a milder one deactivating predominantly the cardiopulmonary receptors (mild LBNP), and a greater one deactivating both the cardiopulmonary and the arterial baroreceptors (strong LBNP). We found that during mild LBNP systemic blood pressure was maintained after acute and chronic ACE inhibition, as in control studies; however, the decrements in forearm blood flow and the increments in forearm vascular resistance caused by LBNP were diminished after ACE inhibition (the latter by 69 and 67%, respectively, in acute and chronic studies), in spite of the fact that the falls in central venous pressure and the increases in noradrenaline (NA) were similar to those observed in control conditions. During strong LBNP, the fall in systemic blood pressure was greater after acute and chronic ACE inhibition than in control conditions and was associated with a reduction in the response of forearm vascular resistance similar to that observed during mild LBNP, while the increments in NA were again superimposable to those seen before ACE inhibition. These alterations in the haemodynamic responses to LBNP induced by ACE inhibition were associated with significant increments in basal plasma renin activity and with marked reductions in Ang II. These findings suggest that even in the sodium-replete state, Ang II exerts a facilitatory action on adrenergic function that is physiologically relevant for the regulation of forearm blood flow and the maintenance of blood pressure during the application of gravitational stresses.

Cardiopulmonary receptor modulation of plasma renin activity in normotensive and hypertensive subjects.

Cardiopulmonary receptors modulate renin release in several animals species. However, their involvement in reflex control of this humoral substance in humans is controversial. Furthermore, no information is available on the alteration of this control in hypertension. We studied the modulation of plasma renin activity (radioimmunoassay) in 12 normotensive subjects and in 12 age-matched subjects with untreated hypertension of mild or moderate degree. Cardiopulmonary receptors were stimulated by increasing central venous pressure (right atrial catheter) and cardiac volume (echocardiographic measurement) through passive leg raising and deactivated by reducing central venous pressure and cardiac volume through lower body negative pressure. The stimuli were maintained for 20 to 30 minutes, and their degree was set to avoid changes in blood pressure (indirect or direct measurements) and heart rate, thus avoiding involvement of arterial baroreceptors. In normotensive subjects, deactivation of cardiopulmonary receptors induced a progressive rise in plasma renin activity and stimulation of cardiopulmonary receptors induced a progressive fall. The reflex gain (ratio between plasma renin activity and central venous pressure or cardiac volume changes) was similar for deactivation and stimulation. During cardiopulmonary receptor deactivation, the gain corresponded to that obtained by dividing the increase in plasma renin by the reduction in central venous pressure induced by tilting. Cardiopulmonary receptor deactivation and stimulation also induced clear-cut changes in plasma renin activity in hypertensive subjects, but the percent magnitude of the reflex plasma renin activity excursion was less than that in normotensive subjects. These observations indicate that cardiopulmonary receptors modulate plasma renin activity in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium antagonists and neural control of circulation in essential hypertension.

Data from animals and from man suggest that calcium antagonists interfere with alpha-adrenergic receptors and that this mechanism may be responsible for some of the vasodilation induced by these drugs. However, alpha-adrenergic receptors play a primary role in baroreceptor regulation of the cardiovascular system and blood pressure homeostasis, which might therefore be adversely affected by calcium antagonist treatment. We addressed this question in 14 essential hypertensives studied before treatment, 1 h after 20 mg oral nitrendipine and 5-7 days after daily administration of 20 mg oral nitrendipine. Blood pressure was measured by an intra-arterial catheter, heart rate by an electrocardiogram, cardiac output by thermodilution and forearm blood flow by venous occlusion plethysmography. Total peripheral and forearm vascular resistances were calculated by dividing mean blood pressure by blood flow values. Plasma norepinephrine was also measured (high performance liquid chromatography) in blood taken from the right atrium. Compared with the pretreatment values, acute nitrendipine administration caused a fall in resting blood pressure, an increase in the resting heart rate and cardiac output, and a fall in resting peripheral and forearm vascular resistance. The resting hypotension and vasodilation were also evident during the prolonged nitrendipine administration, which was, however, accompanied by much less resting cardiac stimulation than that observed in the acute condition. Baroreceptor control of the heart rate (vasoactive drug method) was similar before and after acute and prolonged nitrendipine treatment. This was also the case for carotid baroreceptor control of blood pressure (neck chamber technique) and for control of forearm vascular resistance as exerted by receptors in the cardiopulmonary region (lower-body negative-pressure and passive leg-raising techniques).(ABSTRACT TRUNCATED AT 250 WORDS)