Effects of nifedipine on blood pressure and heart rate in conscious neurogenic hypertensive rats

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

Clonidine reduces blood pressure and heart rate oscillations in hypertensive patients.

Short-term fluctuations in blood pressure (BP) and heart rate (HR) were analyzed in a group of eight men with essential hypertension. Indirect finger BP was measured by a Finapres device. Analog-to-digital conversion of the BP was used to determine systolic (SAP), diastolic (DAP), and mean arterial pressure (MAP) and HR every second. The equidistant sampling allowed a direct spectral analysis using a fast Fourier transform algorithm. The effects of an oral dose of clonidine (150 micrograms) were studied in a double-blind, crossover, placebo-controlled study. Clonidine markedly reduced the variability of BP and HR after 90 min as indicated by a reduction in the standard deviations of BP by 36.7% for SAP, 21.0% for DAP, 22.1% for MAP, and 26.0% for HR. At this time clonidine reduced the average BP by 19.7 mm Hg for SAP, 10.6 mm Hg for DAP, 16.0 mm Hg for MAP, and 1.0 beat/min for HR. Spectral profiles of BP and HR illustrated the alterations in the spontaneous oscillations underlying the standard deviation changes. Clonidine dramatically reduced the amplitude of BP and HR oscillations in the mid-frequency region 66-129 mHz, which depends on the activity of the autonomic nervous system. We suggest that an increased sensitivity of the baroreflex is responsible for the apparent better control of BP and HR with clonidine.     

Effects of long-acting propranolol on blood pressure and heart rate in hypertensive Chinese.

In a double-blind, balanced and randomised study we used treadmill exercise to assess the effects of long-acting propranolol (LA propranolol) 160 or 320 mg or placebo, given once daily for 4 weeks, on heart rate (HR) and blood pressure (BP) in 15 Chinese subjects with mild primary hypertension (PHT). We used 24 h ECG monitoring to assess drug effects on HR. Another 18 patients were similarly assessed without exercise. Steady-state plasma propranolol concentrations after LA propranolol 160 and 320 mg were comparable to those after ordinary propranolol 80 and 160 mg daily measured in 11 and 12 separate patients. LA propranolol 160 and 320 mg reduced HR and BP before and during vigorous exercise. LA propranolol 160 and 320 mg reduced HR for 17.6 and 21.4 h of the day, and 320 mg significantly reduced the mean 24 h HR, and the mean maximum HR. The drug effects on BP and HR, and the average plasma propranolol levels after LA propranolol were similar to those reported in European subjects.     

Effects of dilevalol,an R,R-isomer of labetalol,on blood pressure and renal function in patients with mild-to-moderate essential hypertension

Summary The effects of oral dilevalol (an R, R-isomer of labetalol), a new -adrenoceptor blocker with ₂-receptor stimulating and -recepter blocking properties on blood pressure, renal function, plasma renin activity (PRA) and plasma aldosterone have been studied in 15 patients with mild-to-moderate essential hypertension treated with it for 6 weeks.Two patients with apparent treatment failure and one patient who developed muscle pain and cramps, and had an elevated creatine phosphokinase level, were excluded from the study.Dilevalol monotherapy 100 mg once daily for 6 weeks significantly lowered both the systolic and diastolic blood pressure compared to placebo. Total renal vascular resistance was significantly reduced, and RBF and GFR remained unchanged. Dilevalol significantly decreased PRA.The results suggest that prolonged daily treatment with dilevalol preserves renal function and produces a concomitant hypotensive action in patients with mild-to-moderate essential hypertension. The ancillary pharmacological properties of dilevalol rather than PRA suppression may be relevant to its renal effects.     

Combination of lisinopril and nifedipine GITS increases blood pressure control compared with single drugs in essential hypertensive patients

The present study was designed to evaluate the effect of combination therapy using the angiotensin-converting enzyme-inhibitor lisinopril and the dihydropyridine calcium antagonist nifedipine GITS on the degree and homogeneity of 24-hour blood pressure reduction in essential hypertensive patients. After a 4-week placebo run-in period, 51 patients (mean age, 54.4 +/- 9.4 years) with essential hypertension and clinic diastolic blood pressure between 105 and 115 mm Hg were randomized to 4-week treatment with lisinopril (20 mg), nifedipine GITS (30 mg), or their combination according to a multicenter, randomized, double-blind, crossover study. Trough clinic blood pressure and 24-hour ambulatory blood pressure were measured at the end of the run-in period and after 4 weeks of treatment. In addition to clinic and 24-hour average blood pressure reduction, the trough-to-peak ratio and the smoothness index, a new measure for the homogeneity of blood pressure reduction, were also calculated. Although both lisinopril and nifedipine GITS produced a significant reduction in clinic and 24-hour average blood pressure values, the reduction obtained with the combination was significantly (P < 0.001) greater. Moreover, the combination therapy increased (P < 0.01) the smoothness index as compared with each single drug for both systolic (lisinopril, 1.02; nifedipine GITS, 1.1; combination, 1.76) and diastolic (lisinopril, 0.98; nifedipine GITS, 0.87; combination, 1.54) blood pressure values, whereas trough-to-peak ratio values (expressed as median) for systolic (lisinopril, 0.41; nifedipine GITS, 0.52; combination, 0.55) and diastolic (lisinopril, 0.35; nifedipine GITS, 0.40; combination, 0.49) blood pressure values were not significantly increased by the combination therapy. Thus, antihypertensive treatment with the combination of lisinopril and nifedipine GITS is more effective and balanced over the 24 hours than the combination components administered alone, confirming that the smoothness index is superior to the trough-to-peak ratio in assessing homogeneity of pharmacologic blood pressure reduction.     

Effects of verapamil on blood pressure and heart rate in neurogenic hypertensive rats

The mechanism(s) underlying the prolactin (PRL)-releasing effect of benserazide (Bz), a peripheral inhibitor of L-aromatic amino-acid decarboxylase, was investigated in the rat. In intact male and female rats, Bz was ineffective to increase significantly plasma PRL at 0.8 mg/kg i.p. but elicited an already maximal effect at 1.6 mg/kg. Bz added to in vitro incubated anterior pituitaries (APs) did not alter PRL secretion at the dose of 3.8 X 10(-6)M but increased PRL release at 10(-4)M. Bz, even at very high doses (up to 10(-3) M), did not displace [3H]spiroperidol binding from AP membrane preparations. In rats having had mechanical ablation of the medio basal hypothalamus (MBH), Bz (15 mg/kg i.p.) induced no rise in plasma PRL and did not counteract the striking inhibitory effect of a dopamine (DA) infusion (5 micrograms/kg per min per 120 min). Administration of Bz (15 mg/kg i.p.) into intact male rats decreased significantly the DA concentrations in the median eminence (ME) but not in the residual hypothalamus and the AP. In the same rats 1-dopa (50 mg/kg i.p.) increased significantly the DA concentrations not only in the ME but also in the hypothalamus and the AP. Bz given concurrently with 1-dopa markedly reduced the rise in DA concentrations induced by 1-dopa in the ME, and greatly potentiated the increase in DA concentrations in the hypothalamus. These data indicate that the mechanism whereby a single administration of Bz increases PRL secretion in the rat is not consistent with the postulated DA receptor antagonist action of the drug, but instead implies inhibition of the decarboxylation of 1-dopa at dopaminergic nerve terminals of the ME.     

Influence of nicardipine on the blood pressure at rest and on the pressor responses to cold, isometric exertion, and dynamic exercise in hypertensive patients

The dose-response effects of a new slow-calcium-channel blocker, nicardipine, on the resting blood pressure and on the pressor responses induced by skin cold, isometric exertion, and dynamic exercise were examined in a single-blind placebo-controlled study in six male patients with stable uncomplicated essential hypertension. Nicardipine was administered orally in doses of 5 mg, 10 mg, 20 mg, and 20 mg each given three times daily consecutively for 1 week. At the end of each dose period the effects on blood pressure and heart rate at rest and during the three pressor stimuli were measured. There was a significant dose-related reduction in the resting diastolic blood pressure without change in pulse pressure, accompanied by an increase in heart rate. No postural effects on blood pressure were observed. There was a small reduction in the pressor response to hand cold, which was statistically significant at the higher doses. There was no attenuation of the increases in pressure and heart rate induced by handgrip contraction or submaximal treadmill walking at any dose of nicardipine. These results are compatible with direct relaxing effect of the drug on the smooth muscle of the arteriolar resistance vessels without substantial impairment of the sympathetic influences responsible for postural control of the systemic blood pressure or those involved in the pressor responses to the three stimuli tested.     

Effects of benidipine hydrochloride (Coniel) on blood pressure, heart rate and plasma norepinephrine concentration in spontaneously hypertensive rats]

We investigated the effects of benidipine hydrochloride (benidipine, Coniel) on blood pressure, heart rate and plasma norepinephrine (NE) concentration in spontaneously hypertensive rats and compared them with those of other calcium channel blockers. Benidipine (2 mg/kg, p.o.) was compared with the equihypotensive doses of nifedipine (5 mg/kg), cilnidipine (6 mg/kg) and amlodipine (3 mg/kg). All the 4 calcium channel blockers exhibited significant antihypertensive effects. Nifedipine and cilinidipine significantly increased heart rate, as compared with that in the control group, whereas benidipine or amlodipine did not significantly affect it. The area under the curves for hypotensive effect and tachycardic effect for 10 hr after the drug administration were compared among the 4 compounds. As a result, the tachycardic effect of benidipine was significantly lower than those of nifedipine, cilnidipine and amlodipine, while the hypotensive effects were similar among the 4 compounds. Nifedipine and amlodipine, significantly increased plasma NE concentration, cilnidipine tended to increase it. In contrast, benidipine did not significantly affect plasma NE concentration. These results suggest that the effects of benidipine on plasma NE concentration and heart rate are less prominent than those of the other calcium channel blockers.     

A comparative study of nebivolol and (S) atenolol on blood pressure and heart rate on essential hypertensive patients

Objectives:

To study the effect of nebivolol 5 mg once daily versus (S)-atenolol 25 mg once daily in patients with essential hypertension.

Materials and Methods:

A prospective study was conducted at RLJH and Research Centre which included 30 patients in each group with essential hypertension. The sex, age, presenting illness, and family history of the patients were recorded. Investigations such as blood sugar, urine analysis, kidney function test, lipid profile, and ECG were performed before starting the treatment. Any adverse effects during the treatment were noted. Blood pressure and heart rate were recorded at baseline and during follow-up. One group received nebivolol 5 mg once daily and other group (S)atenolol 25 mg once daily. Patients were followed-up every 15 days for 3 months.

Results:

Nebivolol group had 18 males and 12 females with mean age 50.6 ± 9.5 years, (S)-atenolol had 16 males and 14 females with mean age 54.4 ± 9 years. Patients receiving nebivolol and (S)-atenolol showed a significant fall (P <·0001) in systolic (SBP), diastolic blood pressure (DBP), and heart rate at the end of first, second, and third month when compared to baseline. The difference in fall in SBP and DBP was insignificant between the groups, but fall in heart rate was significant (P <·0001). Adverse effects such as headache, dizziness, and fatigue were reported with both drugs.

Conclusion:

Reduction of blood pressure with nebivolol and (S)atenolol was similar, but fall in blood pressure from baseline was highly significant in both groups.     

Control of blood pressure in hypertensive patients with felodipine extended release or nifedipine retard.

1. This multicentre hospital study compared the antihypertensive efficacy and the tolerability of once daily felodipine extended release (ER) with twice daily nifedipine retard (R) in hypertensive patients inadequately controlled on metoprolol monotherapy. 2. One hundred patients, aged 20-70 years, whose seated diastolic blood pressure was 100-115 mmHg after 4 to 6 weeks of metoprolol (200 mg day-1) monotherapy, were randomised, double-blind, to receive felodipine ER 10 mg once daily or nifedipine R 20 mg twice daily for 8 weeks. The dosage of felodipine or nifedipine was doubled if seated diastolic blood pressure exceeded 95 mmHg, 2 or 4 weeks after randomisation. Metoprolol 200 mg once daily was taken throughout the trial. 3. Fifty-one patients received felodipine ER and 49 nifedipine R; 46 and 45 respectively completed the 8 week trial. About half of patients on each treatment needed the higher dose. The baseline characteristics of the felodipine and nifedipine groups were generally well balanced. 4. Seated diastolic blood pressure was reduced by 17 mmHg for felodipine (24 h post-dose) and by 9 mmHg for nifedipine (12 h post-dose), a difference between treatments of 8 mmHg (95% confidence interval 5 to 12 mmHg, P less than 0.0001). The attained blood pressures at the end of the study (felodipine 90 +/- 10, mmHg, mean +/- s.d.; nifedipine 95 +/- 10) were also significantly different (95% confidence interval for the 5 mmHg difference, -9 to -1 mmHg, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of labetalol and propranolol on blood pressure at rest and during isometric and dynamic exercise

Summary The influence of intravenous labetalol and propranolol on the blood pressure response to isometric and dynamic exercise was examined in a double blind study in eight, young, normotensive volunteers. Effects were recorded after propranolol 7.5, 15 and 30 mg i. v., and after labetalol 30, 60 and 120 mg i. v. In control experiments saline was administered. Mean blood pressure rose with successive handgrip tests following saline and propranolol, but not after labetalol, and the difference was significant. The total dose of each drug produced the same reduction in heart rate during sub-maximal bicycle exercise. The exercise-induced systolic blood pressure response did not differ between the drugs.     

Effect of alacepril on blood pressure and neurohumoral factors at rest and during dynamic exercise in patients with essential hypertension.

We assessed blood pressure and neurohumoral factors at rest and during exercise in 10 patients with essential hypertension before and after treatment with the new angiotensin converting enzyme inhibitor, alacepril (25-50 mg day-1). Alacepril significantly lowered mean blood pressure at rest and at the same exercise load as before treatment without affecting heart rate response. The response of plasma renin activity, plasma aldosterone, and plasma adrenaline were not changed by alacepril, but increase of plasma angiotensin II and plasma noradrenaline during exercise were significantly attenuated after alacepril treatment (ANOVA, P = 0.04, both). The change in mean blood pressure during exercise was positively correlated with the decrease in plasma angiotensin II (r = 0.65, P < 0.05). These results demonstrated that alacepril was effective in essential hypertension both at rest and during exercise, suggesting that the antihypertensive effect during exercise might be related to the decrease in pressor hormones, especially in plasma angiotensin II.     

Effects of concentrated ambient particles on heart rate, blood pressure, and cardiac contractility in spontaneously hypertensive rats

Epidemiological studies have shown that particulate matter (PM) air pollution is associated with cardiovascular mortality and morbidity, especially for particles with aerodynamic diameters under 2.5 microm (PM(2.5)). Recent studies have revealed an association between PM pollution and autonomic functions including heart rate (HR), blood pressure (BP), and heart-rate variability. However, the association and linking mechanisms have not been clearly demonstrated in animal studies. Utilizing a novel approach that employs a mixed-effects model to overcome the problems of variations in diseased animals and circadian cycles, we have previously demonstrated an association between concentrated PM(2.5) and changes of HR and BP in pulmonary hypertensive rats. The objective of this study is to test the plausibility of this methodology and to demonstrate the particle effects under different pathophysiology. The feasibility of cardiac contractility (measured as QA interval, QAI) as an indicator for PM toxicology was also explored. Four spontaneously hypertensive (SH) rats were repeatedly exposed to concentrated PM(2.5) during spring and summer. The mass concentration of particles during the 5 h of exposure was 202.0 +/- 68.8 (mean +/- SE) and 141.0 +/- 54.9 microg/m(3) for spring and summer experiments, respectively. During spring exposures, the maximum increase of HR and mean BP noted at the end of exposure were 51.6 bpm (p <.001) and 8.7 mm Hg (p =.002), respectively. The maximum decrease of QAI noted at the same time was 1.6 ms (p =.001). Though a similar pattern was demonstrated during summer exposures, the responses were less prominent. We conclude that concentrated PM(2.5) may increase HR and mean BP and decrease QAI in SH rats. Our results also show that QAI may be used as an indicator in PM toxicology.     

Effects of vasopressin and V1 receptors blockade on blood pressure and heart rate in spontaneously hypertensive rats.

The aim of the present study was to compare effects of intravenous infusion of vasopressin AVP and V1 receptors blockade on blood pressure and heart rate in normotensive (WKY) and spontaneously hypertensive (SHR) rats. A 20 min vasopressin infusion (1.2 ng/kg/min) elicited significantly greater increase in mean blood pressure (MP) in SHR than in WKY. Heart rate was significantly reduced in SHR while nonsignificantly in WKY. A 20 min dEt2 AVP (V1 antagonist) infusion (0.5 microgram/kg/min) elicited significant decrease in MP and increase in heart rate (HR) in SHR, but produced no effect in WKY. The data indicate that SHR are more susceptible to pressor and hypotensive effects of sustained elevation of AVP and AVP antagonist. The results support the hypothesis that AVP may contribute to pathogenesis of hypertension.     

Effects of nifedipine retard on heart rate and autonomic balance in patients with ischemic heart disease

The aim of this study was to explore the effects of nifedipine retard on heart rate and autonomic balance in patients with ischemic heart disease. Fourteen patients with ischemic heart disease (12 men and two women; mean age 64 years) were administered nifedipine retard at a daily dose of 20-40 mg. Changes in heart rate and autonomic balance were studied using Holter monitoring before and after 12 weeks of nifedipine therapy Heart rate was unchanged during sleep but was higher during the day after nifedipine retard administration. The high frequency power spectrum of heart rate variability (indicating parasympathetic activity) was lower during the day after nifedipine retard therapy but was unchanged during sleep. The low frequency power to high frequency power ratio, indicating sympathetic activity was unchanged during the day and during sleep. Nifedipine retard increased the heart rate of patients with ischemic heart disease only during the day and reduced parasympathetic activity.     

伊贝沙坦对原发性高血压的疗效及心率变异性的影响

目的 :观察伊贝沙坦对原发性高血压 (EH)的疗效及心率变异性的变化。方法 :原发性高血压患者 40例每日口服伊贝沙坦 1 5 0～ 3 0 0mg,共 8wk。观察血压变化 ,记录用药前后 2 4h动态心电图 ,分析心率变异 (HRV)时域和频域指标 ,并与 3 5例健康对照组比较。结果 :①EH患者应用伊贝沙坦后收缩压 (SBP)和舒张压 (DBP)由 2 1 .62± 0 .47/1 2 .0 1±0 .3 2kPa分别下降至 1 8.9± 0 .3 2 /8.0 1± 2 .3 5kPa,有效率达 73 .1 %。②与对照组相比 ,EH患者相邻正常RR间期标准差 (SDNN) ,正常相邻RR间期差值 (RMSSD) ,相邻正常RR间期差值大于 5 0ms的窦性心律 (PNN50 ) ,高频功率 (HF)明显下降 ,低频功率(LF)不变 ,低频功率 /高频功率 (LF/HF)值增加。应用伊贝沙坦后 ,SDNN、RMSSD、PNN50 、HF增加 ,LF/HF值降低。结论 :原发性高血压患者存在HRV下降 ,而伊贝沙坦在有效降低血压同时提高HRV ,改善自主神经功能失衡。     

Effects of phentolamine,dihydroergocristine and isoxsuprine on the blood pressure and heart rate in normotensive,hypotensive and hypertensive rats

Summary Phentolamine, dihydroergocristine and isoxsuprine were compared for their effects on the blood pressure in anaesthetized normotensive rats, in rats made hypotensive by ganglionic blockade or by pithing and in rats with noradrenaline-induced hypertension. Their ability to inhibit pressor responses elicited by electrical stimulation of the posterior hypothalamus and of the sympathetic outflow from the spinal cord was also investigated.All three drugs appeared very potent in inhibiting noradrenaline-induced hypertension and caused a dose-dependent fall in blood pressure in normotensive rats, which however was less pronounced with dihydroergocristine than with phentolamine and isoxsuprine. In hypotensive rats, dihydroergocristine caused a rise in blood pressure.At higher doses than those required to block noradrenaline-induced hypertension, the three drugs inhibited pressor responses elicited by electrical stimulation and were equally active on peripherally- and centrally-evoked responses.Simultaneous recording of heart rate and blood pressure, both in anaesthetized and in pithed rats, indicated a reflex origin for phentolamine-induced tachycardia and a direct cardiac stimulation for isoxsuprine. Reflex changes of heart rate were not observed with dihydroergocristine.     

硝苯地平控释片氨氯地平对原发性高血压患者血压和心率变异性的影响

目的 :研究长效二氢吡啶类钙拮抗剂硝苯地平控释片与氨氯地平在治疗原发性高血压时对血压、心率变异性的影响。方法 :40例原发性高血压患者随机分为硝苯地平控释片组 (n=2 0 )及氨氯地平组 (n=2 0 ) ,分别予硝苯地平控释片 30～ 6 0mg/ d或氨氯地平 5～ 10 mg/ d,共 8wk。治疗前后行 HRV检测 ,并做对比分析。结果 :2组经 8wk治疗后血压均非常显著下降 (P<0 .0 1)。 2组治疗前后 HRV时域 6项指标 ,包括平均 R- R间期 (AVGR- R)、平均 R- R间期标准差 (SDAR- R)、平均 R- R间期的变异系数 (CV)、平均 R- R间期标准差的均值 (SD)、平均 R- R间期标准差的标准差 (SDSD)、相邻 R- R间期差值平方根的均值 (rm SASD)及频域 4项指标 ,包括低频 (L F 0 .0 2 5～ 0 .1Hz)、中频 (MF 0 .1～ 0 .2 Hz)、高频 (HF 0 .2～ 0 .3Hz)、低频 /高频 (R:L F/ HF)均无变化 (P>0 .0 5 )。结论 :长效二氢吡啶类钙拮抗剂治疗原发性高血压病 ,在降血压时对心率变异性无不利影响。     

Effects of cold exposure on blood pressure, heart rate and forearm blood flow in normotensives during selective and non-selective beta-adrenoceptor blockade.

Haemodynamic effects of a cold pressor test (foot immersion for 6 min in water at 5 degrees C) without medication and after the non-selective beta-adrenoceptor blocker propranolol and the selective beta-adrenoceptor blocker metoprolol were studied in 17 volunteers. In the control study as well as in the study with the beta-adrenoceptor blockers cold exposure caused comparable changes, namely a blood pressure rise and a reduction of forearm blood flow. The increase in heart rate during cold exposure was clearly and equally reduced by both beta-adrenoceptor blockers. Plasma noradrenaline rose significantly by 47%, plasma adrenaline did not change. It is concluded, that as to this kind of stress, beta 1-selective-adrenoceptor blockade confers no important advantage over non-selective beta-adrenoceptor blockade.