R. Fariello

Antihypertensive and humoral effects of verapamil and nifedipine in essential hypertension.

The aim of this study was to investigate and compare the effects of two calcium antagonist drugs, verapamil (VER) and nifedipine (NIF), on blood pressure (BP), heart rate (HR), plasma catecholamines (pCA), renin (PRA), plasma aldosterone (pALD), and plasma volume (PV) in a group of patients with mild to moderate essential hypertension. In 12 hypertensive patients on a fixed normal sodium and potassium intake, VER (80 mg t.i.d., per os) first and then NIF (10 mg, t.i.d. per os), or vice versa according to a random sequence, were each given for 8 days, with an interval of 5 days between the two treatments. Both NIF and VER significantly reduced BP (p less than 0.001); this reduction was quantitatively similar in both treatment schedules. Supine and standing PRA, pALD, and PV were not significantly affected by VER or NIF. HR and pCA were unchanged after VER, whereas they were significantly increased (p less than 0.05, at least) mainly in standing position after NIF treatment. The antihypertensive and metabolic effects of VER (80 mg t.i.d.) and NIF (10 mg t.i.d.) were maintained after chronic treatment (4 months with VER in 10 patients and 2 months with NIF in 12 patients). After 2 months of treatment with VER (160 mg t.i.d.) in 18 patients, BP was further reduced, while pCA were slightly increased. In conclusion, VER and NIF are effective and equipotent antihypertensive agents that do not induce significant renin stimulation or fluid retention; adrenergic stimulation seems to be greater with NIF, which should be taken into account in the clinical use of these drugs.

Snoring and risk of cardiovascular disease

In order to evaluate the possible role played by snoring as a risk factor for cardiovascular disease, we studied 400 patients aged 30-80 years, divided into 4 groups matched for age, sex and body mass index. The first group consisted of 100 patients who snored, having risk factors (hypertension, diabetes, obesity, smoking, high serum cholesterol level) for cardiovascular disease. The second group consisted of 100 non-snoring patients with risk factors. The third and fourth groups were formed by 100 snoring and 100 non-snoring patients without risk factors. We investigated the morbidity and the mortality from cardiovascular disease over a period of five years (1982-1987). An increase in morbidity and mortality was found for snorers with risk factors (36 and 17 respectively) compared to non-snorers with risk factors (10 and 4, P less than 0.001), and also to both snorers and non-snorers without risk factors (7 and 3, P less than 0.001; 3 and 1, P less than 0.001 respectively). No difference was noted between snorers and non-snorers without risk factors. A higher morbidity and mortality for cardiovascular disease was found in snorers with risk factors as compared with non-snorers having risk factors. Furthermore, the morbidity and mortality in patients without risk factors was found to be lower compared with that found in snorers with risk factors. In conclusion, snoring worsened the prognosis of patients with risk factors for cardiovascular disease, but did not represent an independent or predictive risk factor in itself.

Effect of pinacidil on blood pressure, plasma catecholamines and plasma renin activity in essential hypertension.

SummaryPinacidil, a new cyanoguanidine derivative, is an antihypertensive agent with arteriolar vasodilating properties, which acts on precapillary resistance vessels. A trial was carried out in 30 patients with essential hypertension WHO I-II. The treatment period was divided into three phases. Hydrochlorothiazide (HCTZ) and amiloride were administered for 4 weeks in Phase 1 and supine and standing blood pressure decreased significantly. During Phase 2 pinacidil was added to HCTZ/amiloride for the following 3 months. A further significant reduction in blood pressure was obtained. In the next period of treatment (Phase 3) patients were divided into two groups. For 1 month Group A (15 patients) received pinacidil alone and Group B (15 patients) received HCTZ/amiloride. Conventional laboratory blood tests in all patients remained unchanged during treatment. Reported side effects during Phase 2 were headache (2 patients), dizziness (3 patients), palpitations (2 patients) and ankle oedema (2 patients). Plasma renin activity was slightly increased at the end both of Phases 1 and 2. Plasma catecholamines were increased but not significantly at the end of Phase 2 as compared to Phase 1. The results indicate that pinacidil is effective in lowering blood pressure in mild to moderate essential hypertension.

Effect of enalapril on parasympathetic activity.

SummaryTo evaluate the effect of converting enzyme inhibition induced by enalapril on parasympathetic activity, we studied ten essential hypertensive patients, age range 38–58 years, WHO I–II. Parasympathetic evaluation was obtained by measuring the variation of heart period (VHP) during at least 1 minute of steady-state, regular respiration. VHP was derived from the difference between the mean of all maximum and the mean of all minimum heart periods. The higher the VHP, the higher the parasympathetic control of heart rate and vice versa. VHP was measured supine and with tilting (30°, 60°, 85°). Blood pressure was reduced after 1 month of enalapril treatment, while the heart rate did not change. VHP increased at the end of enalapril treatment compared with placebo: in the supine position it increased from 36±3.2 ms to 44±3.5 ms, p<0.01. VHP was also increased by enalapril at 30° (p<0.05) and 60° (p<0.05), while no difference was observed at 85° between placebo and enalapril. A positive correlation was found between supine enalapril changes of VHP and those of systolic and diastolic BP. In conclusion, enalapril seems to increase parasympathetic cardiovascular control in essential hypertensive patients. This result might explain the lack of increase in heart rate that would be expected as a result of the vasodilating effect of enalapril.

Ibopamine vs. digoxin in chronic heart failure: a double-blind, crossover study.

Ibopamine, a dopamine derivative suitable for oral administration, is reported to improve cardiac function in patients with chronic heart failure. In order to evaluate the inotropic effect of ibopamine and to compare it with that of digoxin, we studied 10 patients with chronic heart failure (NYHA II–III). All patients were in sinus rhythm. After a washout period of 5 days, when the patients received a constant diuretic dosage and a placebo, ibopamine 100 mg t.i.d. or digoxin 0.25 mg o.d. was randomly given double-blind. The active treatment was continued for a 10-day period, and was followed by a second washout period of 5 days. Subsequently, the patients received digoxin if previously on ibopamine or ibopamine if previously on digoxin for 10 days. Diuretic was continued at the same dosage throughout the study. At the end of the two washout periods, all patients performed a static (hand grip) and a dynamic exercise (bicycle ergometer). Both ibopamine and digoxin improved cardiac response to both types of exercise compared to the washout periods. In particular. PEP/LVET decreased (p < 0.001 for both drugs) and O2 consumption improved (from 586 ± 48 to 716 ± 35 ml/min for ibopamine and from 585 ± 38 to 713 ± 52 ml/min for digoxin). No difference was noted between the two drugs in the improvement of exercise tolerance. No side effects were noted with the two drugs. These data indicate that ibopamine could be a valid alternative to digoxin in heart failure patients in sinus rhythm when given for 10 days. More data are needed to evaluate the long-term efficacy of ibopamine.

Ventricular arrhythmias in normotensive subjects and in mild hypertensive patients

Twenty-five normotensive subjects (14 men, 11 women) aged from 25 to 60 years (mean 36) and 30 untreated patients with mild hypertension (stages 1 and 2, JNC V) without target organ damage (16 men, 14 women), aged 26-59 years (mean 35.8) underwent continuous 24-hour ECG Holter monitoring with a Fukuda Denshi SM-40 ambulatory recorder and SCM-400 ECG analyzer. During 24-hour ambulatory ECG recording, mean heart rate was slightly but not significantly higher in hypertensive patients (73.3 ± 10 beats per minute [bpm]) in comparison with normotensive subjects (71.2 ± 12 bpm). The prevalence of premature atrial contractions was similar in the two groups. Total ventricular arrhythmias were more prevalent in the group of mild hypertensive patients (P<0.05), who also had a higher prevalence in complex forms of ectopy (r=0.81 for bigeminy; r=0.83 for trigeminy; r=0.83 for couplets). Holter recordings did not show abnormalities of ST-T wave or episodes of silent ischemia.

Ambulatory-determined 24-hour blood pressure in mild hypertensives and in normotensives

Noninvasive ambulatory twenty-four-hour blood pressure (BP) monitoring was carried out in 30 normotensive subjects (16 women, 14 men), aged twenty-five to sixty years (mean thirty-eight) and in 29 mild essential hypertensive patients without target organ damage (14 women, 15 men), aged twenty-three to sixty-one years (mean thirty-nine). Hypertensive patients were not treated, and they discontinued any antihypertensive treatment at least four weeks before the study. During the daytime period (6 AM-10 PM) BP was monitored every fifteen minutes, and during the night (10 PM-6 AM), every thirty minutes. Obviously, mean twenty-four-hour systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher in hypertensive patients (P < 0.001). There was a persistent correlation in the group of mild hypertensives between successive BP hourly mean readings (r ranged from 0.61 to 0.93 for SBP and from 0.45 to 0.82 for DBP). In normotensive subjects these correlations failed in particular periods: 8 AM-9 AM, r = 0.30 for SBP and 0.45 for DBP; 1 PM-3 PM, r = 0.17-0.49 for SBP and 0.28-0.37 for DBP; 9 PM to midnight, r = 0.21-0.57 for SBP and 0.23-0.38 for DBP.

Effect of Enalapril at Rest and During Isometric and Dynamic Exercise in Essential Hypertensive Patients

Vasodilator drugs reduce peripheral vascular resistance but lead to a secondary baroreflex-mediated chronotropic effect. After angiotensin-converting enzyme inhibition, blood pressure falls without associated tachycardia. In a previous study it was observed that enalapril increased vagal tone in essential hypertensive patients. In order to evaluate the effect of enalapril on sympathetic stimulation 10 mild to moderate hypertensive patients were studied during static (hand grip) and dynamic exercise (bicycle ergometer), after 2 weeks of placebo and after 1 month of treatment with 20–40 mg enalapril once daily. Enalapril significantly reduced blood pressure and the rate–pressure product at rest and at peak dynamic exercise. There was no effect on supine and maximal heart rate. Enalapril also significantly reduced blood pressure during hand grip, but did not interfere with the rate of the increase. Thus, enalapril does not seem to interfere with sympathetic adaptation to stress.