Long-term outcomes after angioplasty of isolated, below-the-knee arteries in diabetic patients with critical limb ischaemia.

BACKGROUND: It has been shown that concomitant percutaneous transluminal angioplasty (PTA) of above-the-knee (ATK) and below-the-knee (BTK) arteries is highly beneficial for limb salvage in patients with critical limb ischaemia (CLI), but few published studies have specifically investigated outcomes in diabetic patients with CLI associated with isolated small BTK-vessel disease. This study aimed to evaluate the long-term results of successful PTA for limb salvage in such patients. MATERIALS AND METHODS: From among the 634 patients with CLI in our database, we retrospectively selected a consecutive series of 101 diabetics (16%) with 107 critically ischaemic limbs (33 Rutherford 5 and 74 Rutherford 6) and no critical ATK lesion, who underwent PTA on isolated BTK lesions. RESULTS: The limb salvage rate was 93% after a mean follow-up of 1048+/-525 days (2.9+/-1.4 years). Transcutaneous oxygen tension significantly increased after 1 month (18.1+/-11.2 vs. 39.6+/-15.1; p<0.05). After 1 year, target-vessel re-stenosis had occurred in 42% of the non-amputated limbs, nine patients (9%) had died because of medical conditions unrelated to PTA and three patients had undergone repeat PTA for recurrent CLI. CONCLUSIONS: In our selected patient population with ischaemic diabetic foot and isolated BTK lesions, a successful endovascular procedure led to a high percentage of limb salvage at long-term follow-up.

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.

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.

The alpha-1 adrenergic blocking agent urapidil counteracts postrotational atherectomy "elastic recoil" where nitrates have failed.

Calcium antagonist pretreatment and intracoronary high doses of nitrates (9 mg of isosorbide dinitrate) do not counteract coronary vasoconstriction occurring after rotational atherectomy. In 30 patients undergoing Rotablator atherectomy, intracoronary injection of the alpha 1-sympathetic blocker urapidil abolished or prevented significant vasoconstriction occurring 15 minutes after the procedure despite repeated injections of nitrates.

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)

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.

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.

Twenty-four hour ambulatory intra-arterial blood pressure in normotensive and borderline hypertensive subjects.

A number of studies have shown that blood pressure values obtained by ambulatory monitoring are lower than those obtained in the doctor's office by cuff readings. However, there is still no suitable information on 'normal' 24-h ambulatory blood pressure values. In 19 normotensive and 13 borderline hypertensive subjects, defined by repeated office blood pressure measurements, we recorded intra-arterial blood pressure under ambulatory conditions for 24 h (Oxford method) in order (1) to assess the 24-h blood pressure values of normal subjects, and (2) to compare their 24-h blood pressure values with those of borderline hypertensive patients. In the normotensive subjects systolic, diastolic and mean ambulatory blood pressure values over 24 h were significantly lower than the corresponding office values, the differences being -15.0, -22.1 and -17.9 mmHg, respectively. In the borderline hypertensives 24-h ambulatory blood pressure was significantly lower than office readings. On average, the 24-h mean blood pressure of normotensive subjects was significantly lower than that of borderline patients (P less than 0.01). However, individual 24-h blood pressure values showed a considerable overlap. Thus, (1) ambulatory blood pressure values just below 140/90 mmHg do not necessarily mean that the blood pressure is in the normal range, the mean 24-h blood pressure of true normotensive subjects being much lower; (2) ambulatory blood pressure monitoring in patients with high office blood pressure readings may help to identify subjects whose 24-h mean values are indistinguishable from those of normotensives. However, the clinical relevance of these findings in the diagnosis of hypertension has to be validated by prospective clinical trials.

24-hour blood pressure monitoring: evaluation of Spacelabs 5300 monitor by comparison with intra-arterial blood pressure recording in ambulant subjects.

The accuracy of 24-h blood pressure values obtained by ambulatory monitoring via the Spacelabs 5300 device was evaluated by comparison with simultaneous 24-h intra-arterial blood pressure recording from the contralateral arm. The comparison was made in eight essential hypertensive subjects in whom non-invasive blood pressure was measured every 15 (day) or 30 min (night). The measurements were automatically and visually edited to eliminate artefactual readings and hourly and 24-h means were calculated separately for systolic and diastolic blood pressure. The corresponding intra-arterial blood pressure means were also calculated. In the group as a whole, hourly means obtained by the non-invasive device were similar or only slightly different from those recorded intra-arterially. The 24-h systolic blood pressure mean obtained non-invasively was not significantly different from that obtained intra-arterially (138.4 +/- 9.1 and 142.9 +/- 9.2 mmHg, respectively), nor were the corresponding 24-h diastolic blood pressure means significantly different (83.5 +/- 4.5 and 80.6 +/- 3.5 mmHg, respectively). However, in spite of these similarities, there were contrasting and often large discrepancies between non-invasive and intra-arterial values in individual subjects. For the 24-h systolic blood pressure mean the discrepancies ranged from 7.6 +/- 1.1 to 16.1 +/- 2.2 mmHg and for the 24-h diastolic blood pressure mean, from 3.5 to 13.2 mmHg. Thus, the Spacelabs 5300 device has a limited ability to correctly estimate ambulatory blood pressure in individual subjects. It may be better suited for the estimation of group blood pressures, but only because errors are smoothed by the summation of individual errors of opposing signs.

Evaluation of the baroreceptor-heart rate reflex by 24-hour intra-arterial blood pressure monitoring in humans.

The baroreceptor control of the sinus node was evaluated in 10 normotensive and 10 age-matched essential hypertensive subjects in whom ambulatory blood pressure was recorded intra-arterially for 24 hours and scanned by a computer to identify the sequences of three or more consecutive beats in which systolic blood pressure (SBP) and pulse interval (PI) progressively rose (+PI/+SBP) or fell (-PI/-SBP) in a linear fashion, according to a method validated in cats. In normotensive subjects, several hundred +PI/+SBP and -PI/-SBP sequences of 3 beats were found whereas the number of sequences of 4, 5, and more than 5 beats showed a progressive drastic reduction. The mean slopes of +PI/+SBP (7.6 +/- 2.0 msec/mm Hg) and -PI/-SBP (6.4 +/- 1.5 msec/mm Hg) sequences were similar, but in both instances there was a large scattering of the values around the mean (variation coefficients: 64.2 +/- 4.7 and 62.6 +/- 2.4%). The slopes decreased as a function of the sequence length and baseline heart rate and increased to a marked extent during the night as compared with daytime values. All sequences were more rare (-33.2% for +PI/+SBP and -31.7% for -PI/-SBP) and less steep in hypertensive subjects (-40.3 and -36.2%, respectively), who failed to show the marked nighttime increase in slope observed in normotensive subjects. To our knowledge, these observations provide the first description in humans of the baroreceptor-heart rate reflex in daily life. This reflex is characterized by marked within-subject variations in sensitivity due in part to hemodynamic, temporal, and behavioral factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the cardiovascular effects of different laboratory stressors and their relationship with blood pressure variability.

Laboratory stressors are employed to assess the 'typical' cardiovascular reactivity to stress of a given subject. It is believed that this may assist in the diagnosis of hypertension and predict future development of blood pressure (BP) elevation. However, the internal consistency of the data obtained by laboratory stressing manoeuvres and their ability to reflect the effects of everyday stressful events occurring over a 24-h period have never been clearly established. We studied a group of ambulant normotensive and essential hypertensive in-patients who were undergoing prolonged intra-arterial blood pressure monitoring (Oxford method) to determine firstly, whether four routine laboratory stressors provided a homogeneous evaluation of subjects' reactivity and secondly, whether cardiovascular reactivity to these stressors reflected a tendency of BP to vary over a 24-h period. A significant correlation (P less than 0.01) was found between the pressor responses to mental arithmetic and the mirror drawing test and between the pressor responses to the cold pressor test and hand-grip. These correlations, however, were not close and responses to the 'mental' and 'physical' stressors were unrelated. The elevation in BP induced by laboratory stressors also did not correlate with the increase in BP accompanying stress elicited outside laboratory conditions (i.e. doctor's visit). The pressor effects of both the laboratory and the out-of-laboratory stressors showed little or no correlation with the 24-h absolute or per cent blood pressure variabilities, although for the stressors involving a mental challenge, a significant though not close correlation with daytime blood pressure variability was found. These data underline the limitations of laboratory tests in assessing cardiovascular reactivity to stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the antihypertensive effect of celiprolol by ambulatory blood pressure monitoring.

The use of ambulatory blood pressure monitoring has gained popularity because it is not subject to those limitations associated with traditional sphygmomanometry (inaccuracy of blood pressure readings, low number of readings, and failure to represent daytime blood pressure readings). In the present study, we provide evidence that the 24-hour mean blood pressure obtained through intraarterial blood pressure measurements in ambulatory patients provides a more accurate diagnosis (and perhaps a prognosis) of hypertension than that provided by cuff-obtained casual blood pressure measurement. Furthermore, despite a reduction in the amount and in the accuracy of the information obtained, blood pressure data provided by noninvasive blood pressure monitoring are also more accurate diagnostically than cuff-obtained casual blood pressure measurements. In 15 essential hypertensive patients in whom celiprolol, 400 mg once daily, was compared with placebo in a randomized double-blind crossover study, the use of noninvasive 24-hour automatic blood pressure monitoring showed that in responsive patients, celiprolol induced a sustained reduction in systolic and diastolic blood pressure throughout the 24 hours. The blood pressure reduction was also apparent during the night, despite the concomitant occurrence of a slight tachycardia. These findings demonstrate that once-daily administration of celiprolol provides an effective lowering of the 24-hour blood pressure profile. This dosing schedule can therefore be regarded as appropriate for antihypertensive therapy.

Neural control of circulation before and after intravenous urapidil in essential hypertension.

Drugs interfering with sympathetic influences on the cardiovascular system have been shown to effectively lower blood pressure in hypertension. However, sympathetic cardiovascular control is involved in blood pressure homeostasis, which means that these drugs may produce potential adverse haemodynamic effects that may reduce the benefit of their antihypertensive action. This paper summarises the results of a study in which we examined the effects of urapidil on the arterial baroreflex and the cardiopulmonary reflex in 6 essential hypertensive patients given 25 mg of the drug intravenously. The dose of the drug used caused a marked reduction in arterial blood pressure (direct measurement). However, pressor and depressor responses to carotid baroreceptor deactivation and stimulation (neck chamber device), respectively, were not modified when compared with those observed in the placebo period. This was also the case for increases and reductions in both forearm vascular resistance and plasma noradrenaline (norepinephrine) concentrations induced by deactivating and stimulating cardiopulmonary receptors, respectively. The pressor and tachycardic responses to handgrip and cold exposure were also unaffected by the drug. It is concluded that when administered at a clinically effective dose urapidil does not adversely affect major reflex mechanisms involved in neural cardiovascular regulation. This has favourable implications for the use of the drug in clinical practice.

24-h ambulatory non-invasive blood pressure monitoring in the assessment of the antihypertensive action of celiprolol.

The well-known limitations of traditional sphygmomanometer blood pressure measurements have led to the development of a number of invasive and non-invasive 24-h blood pressure monitoring techniques which provide information on blood pressure in daily life. A non-invasive portable blood pressure monitor (IRC Spacelab S5300 monitor) was used to assess the antihypertensive action of celiprolol, 400 mg once daily, in a randomized, double-blind, crossover, placebo-controlled study. After a washout period of 7 days, 15 patients with mild or moderate essential hypertension were subjected to three 24-h blood pressure recordings: at the end of washout, and after 1 month of placebo and celiprolol treatment. In the 10 responsive patients, celiprolol reduced 24-h systolic blood pressure, diastolic blood pressure and heart rate by 6.8%, 8.1% and 2.7%, respectively, when compared with placebo. The reduction in blood pressure was also evident during the night and the antihypertensive action of celiprolol was maintained 24-h after administration. Celiprolol had no effect on 24-h blood pressure or heart rate variability and, therefore, did not produce any alteration in cardiovascular homeostasis. These results demonstrate that celiprolol is an effective once daily treatment for hypertension.

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)