Acute Administration Of Nifedipine Research Articles

Cooperation of augmented calcium sensitization and increased calcium entry contributes to high blood pressure in salt-sensitive Dahl rats.

Salt hypertensive Dahl rats are characterized by sympathoexcitation and relative NO deficiency. We tested the hypothesis that the increased blood pressure (BP) response to fasudil in salt hypertensive Dahl rats is due to augmented calcium sensitization in the salt-sensitive strain and/or due to their decreased baroreflex efficiency. BP reduction after acute administration of nifedipine (an L-type voltage-dependent calcium channel blocker) or fasudil (a Rho kinase inhibitor) was studied in conscious intact rats and in rats subjected to acute NO synthase inhibition or combined blockade of the renin-angiotensin system (captopril), sympathetic nervous system (pentolinium), and NO synthase (L-NAME). Intact salt-sensitive (SS) Dahl rats fed a low-salt diet had greater BP responses to nifedipine (-31 ± 6 mmHg) or fasudil (-34 ± 7 mmHg) than salt-resistant (SR) Dahl rats (-16 ± 4 and -17 ± 2 mmHg, respectively), and a high-salt intake augmented the BP response only in SS rats. These BP responses were doubled after acute NO synthase inhibition, indicating that endogenous NO attenuates both calcium entry and calcium sensitization. Additional pentolinium administration, which minimized sympathetic compensation for the drug-induced BP reduction, magnified the BP responses to nifedipine or fasudil in all groups except for salt hypertensive SS rats due to their lower baroreflex efficiency. The BP response to the calcium channel blocker nifedipine can distinguish SS and SR rats even after calcium sensitization inhibition by fasudil, which was not seen when fasudil was administered to nifedipine-pretreated rats. Thus, enhanced calcium entry (potentiated by sympathoexcitation) in salt hypertensive Dahl rats is the abnormality that is essential for their BP increase, which was further augmented by increased calcium sensitization in salt-sensitive Dahl rats.

Nifedipine-Sensitive Blood Pressure Component in Hypertensive Models Characterized by High Activity of Either Sympathetic Nervous System or Renin-Angiotensin System

High blood pressure (BP) of spontaneously hypertensive rats (SHR) is maintained by enhanced activity of sympathetic nervous system (SNS), whereas that of Ren-2 transgenic rats (Ren-2 TGR) by increased activity of renin-angiotensin system (RAS). However, both types of hypertension are effectively attenuated by chronic blockade of L-type voltage-dependent calcium channel (L-VDCC). The aim of our study was to evaluate whether the magnitude of BP response elicited by acute nifedipine administration is proportional to the alterations of particular vasoactive systems (SNS, RAS, NO) known to modulate L-VDCC activity. We therefore studied these relationships not only in SHR, in which mean arterial pressure was modified in a wide range of 100-210 mm Hg by chronic antihypertensive treatment (captopril or hydralazine) or its withdrawal, but also in rats with augmented RAS activity such as homozygous Ren-2 TGR, pertussis toxin-treated SHR or L-NAME-treated SHR. In all studied groups the magnitude of BP response to nifedipine was proportional to actual BP level and it closely correlated with BP changes induced by acute combined blockade of RAS and SNS. BP response to nifedipine is also closely related to the degree of relative NO deficiency. This was true for both SNS- and RAS-dependent forms of genetic hypertension, suggesting common mechanisms responsible for enhanced L-VDCC opening and/or their upregulation in hypertensive animals. In conclusions, BP response to nifedipine is proportional to the vasoconstrictor activity exerted by both SNS and RAS, indicating a key importance of these two pressor systems for actual L-VDCC opening necessary for BP maintenance.

Role of nifedipine-sensitive sympathetic vasoconstriction in maintenance of high blood pressure in spontaneously hypertensive rats: effect of Gi-protein inactivation by pertussis toxin

High blood pressure (BP) in spontaneously hypertensive rats (SHRs) is attributed to excessive activity of sympathetic nervous system (SNS) and relative nitric oxide deficiency. An important part of SNS hypertensive action is exerted by calcium influx through L-type of voltage-dependent calcium channels (L-VDCC). The overexpression of pertussis toxin (PTX)-sensitive inhibitory G-proteins (Gi) participating in the development and maintenance of high BP in SHRs suggested us to study Gi-protein involvement in the pathway through which noradrenergic vasoconstriction and calcium influx can be coupled. The participation of main vasoactive systems (angiotensin II, norepinephrine, nitric oxide) in BP maintenance was investigated in conscious SHR and WKY rats (half of them being pretreated with PTX, 10 microg/kg i.v., 48 h before the experiment). To evaluate the contribution of Gi-proteins and L-VDCC to vasoconstriction induced by exogenous norepinephrine, dose-response curves were determined before and after acute nifedipine administration. PTX pretreatment of SHRs significantly decreased BP and reduced sympathetic vasoconstriction, which was partially substituted by enhanced angiotensin II-dependent vasoconstriction. PTX pretreatment also reduced nitric oxide-dependent vasodilation in both rat strains. PTX pretreatment of SHRs decreased BP component sensitive to acute blockade of calcium entry by nifedipine. In both strains, PTX pretreatment as well as acute nifedipine administration caused substantial rightward shift of norepinephrine dose-response curves (without additive effects of both treatments). The enhanced contribution of SNS to hypertension maintenance in SHRs is mediated by Gi-protein-coupled pathway controlling calcium influx through L-VDCC.

Involvement of hypothalamic pituitary adrenal axis on the nifedipine-induced antinociception and tolerance in rats

Nifedipine, a calcium channel blocker, can modulate the nociceptive threshold. However, the underlying mechanism, especially the role of HPA axis, on this effect has still not been elucidated. In the present study we investigated the analgesic effect of nifedipine in intact and adrenalectomized (ADX) male rats and we also measured the effect of nifedipine on HPA function. The Tail-Flick test was used to assess the nociceptive threshold before and 15, 30, 60, 90, and 120 min after drug administration. Corticosterone level was measured by radioimmunoassay as a marker of HPA function. Our results showed that in intact and sham operated animals, administration of 10 mg/kg nifedipine induces an antinociceptive effect. But at the dosage of 2 and 5 mg/kg animals do not exhibit this effect. With repeated injections, its analgesic effect was decreased, a phenomenon prevented by adrenalectomy. Acute administration of nifedipine produced significant decrease in plasma corticosterone level. In ADX animals, had a potent antinociceptive effect nifedipine at high dosage (10 mg/kg) as well as at lower dosage (5 mg/kg) that reversed with corticosterone replacement. In conclusion, the results of our study show that the elimination of HPA function through adrenalectomy potentiates the antinociceptive effect of nifedipine and attenuates its analgesic tolerance. Both effects are reversed by corticosterone replacement.

Nifedipine improves coronary and peripheral endothelial function in patients with coronary artery disease: Are calcium channel blockers acquitted on the charges?

We have read with great enthusiasm the recently published article by Takase et al. [1]. This meticulously designed study helped us to refocus on calcium channel blockers in the prevention of endothelial dysfunction and atherosclerosis. Takase et al. revealed that acute administration of nifedipine improves not only coronary but also brachial artery vasodilator responses to acetylcholine by using invasive tests in patients with coronary artery disease (CAD). They concluded that nifedipine improves coronary and peripheral endothelial function in patients with CAD. Endothelial dysfunction is thought to play a pivotal role in the development, progression and clinical complications of atherosclerosis [2]. The vascular endothelium has emerged as an attractive treatment target, given accumulating data suggesting an important role of endothelial dysfunction for prognosis in vascular disease including coronary arterial tree. Although calcium channel blockers (CCBs) were developed as vasodilators, with the evolution of second and thirdgeneration CCBs, pleitropic effects have been noticed, and at least some of CCBs' benefit is attributable to these mechanisms [3]. CCBs have been shown to enhance the effects of nitric oxide and diminish those of endothelin-1 on vascular smooth muscle cell improving endothelial function. This phenomenon might be related to the antioxidant properties of some CCBs like amlodipine and nisoldipine [4]. Effect of Nifedipine and Cerivastatin on Coronary Endothelial Function in Patients with Coronary Artery Disease (ENCORE) study showed that combination of nifedipine and cerivastatin improved endothelial function [5].

Beneficial effects of nifedipine on vasodilator response to acetylcholine in coronary and brachial arteries in the patients with coronary artery disease

Background Nifedipine has been reported to improve endothelial function. However, there are few simultaneous studies on the effects of nifedipine on coronary and peripheral endothelial function in humans. Methods To investigate the effects of nifedipine on endothelial function in coronary artery (CA) and brachial artery (BA) in coronary artery disease (CAD), we measured vasodilator responses of CA and BA to acetylcholine (ACh, endothelium-dependent dilation) in 13 patients (63 ± 10 years old) with CAD before and after sublingual administration of nifedipine 10 mg. To measure blood flow, a Doppler guidewire was inserted into the major branch of CA and the left BA. ACh was infused at 10 − 7 mol/l for 3 min into CA and at 15.0 μg/ml for 5 min into BA, respectively. The vasodilator response to ACh was assessed by the ratio of ACh-induced flow / baseline flow (CAVR index, the ratio of CA flow changed by ACh; BAVR index, the ratio of BA flow changed by ACh). Results Nifedipine significantly increased both the CAVR and BAVR index : CAVR index, from 1.33 ± 0.54 to 1.76 ± 0.52 (32%) and BAVR index, from 1.74 ± 0.83 to 2.18 ± 0.93 (25%), respectively, p < 0.05. In addition, nifedipine-induced changes in CAVR tended to correlate with those of BAVR ( r = 0.42. p = 0.06). Conclusions Acute administration of nifedipine improves both coronary and brachial artery vasodilator responses to ACh. Nifedipine improves coronary and peripheral endothelial function in patients with CAD.

Prevention of diazepam withdrawal syndrome by nifedipine—behavioural and neurochemical studies

Our studies aimed at investigating whether the dihydropyridine calcium antagonist, nifedipine, could prevent anxiogenic-like consequences of diazepam withdrawal in rats. Animals withdrawn from chronic diazepam (2 mg/kg/day i.p. for 2 weeks) drank significantly less water than did control rats in the unfamiliar arm of a Y maze. This anxiogenic-like effect could be prevented by acute administration of nifedipine (at 10 mg/kg i.p., but not at lower doses), which, on its own, did not change water intake in naive rats. Given chronically in combination with diazepam for the second half of a 2-week treatment with this drug, nifedipine (at the daily dose of 5 mg/kg i.p.) also suppressed the reduction of water intake normally observed on diazepam withdrawal. Biochemical measurements showed that acutely, as well as chronically, administered nifedipine increased 5-HT turnover in the hippocampus of diazepam-treated rats, thereby suggesting that the prevention of diazepam withdrawal-induced anxiogenic behaviour by the calcium antagonist might be underlain by serotoninergic mechanisms.

Radionuclide monitoring of left ventricular function after sublingual nifedipine administration at rest and during moderate physical activity

Background. This study investigates the acute effects of nifedipine administration on left ventricular (LV) function in patients with different degrees of heart failure at a fixed heart rate under resting conditions and during moderate physical activity. Methods and Results. Eleven patients with non-rate-responsive DDD pacemakers were studied. According to baseline LV ejection fraction, patients were divided into 2 groups: 6 patients with an ejection fraction of less than 50% (group 1) and 5 patients with an ejection fraction of 50% or more (group 2). LV function was monitored by a radionuclide system (Vest) at rest and during moderate physical activity (10-minute walk test) before and after sublingual nifedipine administration (10 mg). In all patients, both the systolic blood pressure and diastolic blood pressure were significantly reduced (P < .05) 6 minutes after nifedipine administration. In group 1, end-diastolic volume and ejection fraction decreased after 3 minutes and remained significantly lower (P < .05) than resting values until 10 minutes after drug administration, whereas end-systolic volume was unchanged. In group 2, nifedipine induced a minor decrease in end-diastolic volume and a slight but not significant decrease in ejection fraction and end-systolic volume. During the walk test, nifedipine induced similar changes in all parameters of cardiac performance in both groups. Conclusions. In patients with impaired LV function, acute nifedipine administration has a negative effect on cardiac performance, which occurs before blood pressure reduction. On the other hand, during moderate physical activity, nifedipine does not affect the improvement in LV function. (J Nucl Cardiol 2001;8:669-76.)

Comparison of the Effects of Nitric Oxide, Nitroprusside, and Nifedipine on Hemodynamics and Right Ventricular Contractility in Patients With Chronic Pulmonary Hypertension

The effects of inhaled nitric oxide (NO) on hemodynamics and right ventricular (RV) contractility were compared with those of nitroprusside and nifedipine in 14 patients with severe chronic pulmonary hypertension. Micromanometer and balloon-tipped right heart catheterization were performed. Inhaled NO, IV nitroprusside, and sublingual nifedipine were administered sequentially while patients breathed > 90% oxygen. Cardiac catheterization laboratory in a tertiary care teaching hospital. Fourteen patients with severe pulmonary hypertension unrelated to left ventricular dysfunction. During NO inhalation, mean systemic arterial pressure (MAP) was unchanged, but pulmonary artery (PA) pressure ([mean +/- SEM] 49 +/- 2 mm Hg vs 44 +/- 2 mm Hg; p < 0.01), pulmonary vascular resistance (PVR; 829 +/- 68 vs 669 +/- 64 dyne x s x cm(-5); p < 0.01) and RV end-diastolic pressure (RVEDP; 12 +/- 1 vs 10 +/- 1 mm Hg; p < 0.01) decreased. Stroke volume index (SVI; 31 +/- 2 vs 35 +/- 3 mL/m(2); p < 0.05) increased, and the first derivative of RV pressure at 15 mm Hg developed pressure (RV +dP/dt at DP15) was unchanged. During nitroprusside administration, MAP decreased (105 +/- 5 vs 76 +/- 5 mm Hg; p < 0.01), PA was unchanged (48 +/- 2 vs 45 +/- 3 mm Hg; p = not significant), and PVR decreased (791 +/- 53 vs 665 +/- 53 dyne x s x cm(-5); p < 0.01). RV +dP/dt at DP15 increased (425 +/- 22 vs 465 +/- 29 mm Hg/s; p < 0.05), but SVI was unchanged. Nifedipine decreased MAP (103 +/- 5 vs 94 +/- 5 mm Hg; p < 0.01), PA and PVR were unchanged, RVEDP increased (12 +/- 1 vs 14 +/- 2 mm Hg; p < 0.01), and RV +dP/dt at DP15 decreased (432 +/- 90 vs 389 +/- 21 mm Hg/s; p < 0.05). Inhaled NO is a selective pulmonary vasodilator in patients with chronic pulmonary hypertension that improves cardiac performance without altering RV contractility. Nitroprusside caused a similar degree of pulmonary vasodilation. In contrast to inhaled NO, nitroprusside caused systemic hypotension associated with an increase in RV contractility. Acute administration of nifedipine did not cause pulmonary vasodilation, but RVEDP increased and RV contractility decreased.

Role of calcium channels in effects of antidepressant drugs on responsiveness to pain.

The effect of acute and chronic treatment with three antidepressant drugs on the cortical L-type calcium channel (measured as [3H]nitrendipine binding sites) and on the responsiveness to pain (assessed in the hot-plate test) was tested on the Wistar rat. Acute administration of antidepressants did not affect the characteristics of calcium channels and did not significantly prolong the hot-plate latency. However, a combination of antidepressants with nifedipine brought about analgesia. Chronic administration of imipramine did not significantly affect the characteristics of calcium channels but produced a moderate analgesic effect. In contrast, chronic administration of citalopram and chlorprothixene increased the density of [3H]nitrendipine binding sites and induced hyperalgesia, which was nullified by acute administration of nifedipine. The results confirm that calcium channels may be involved in analgesia and hyperalgesia and indicate that chronic treatment with some antidepressant may induce an increase in the density of cortical calcium channels.

Effects of nifedipine on left ventricular diastolic function in hypertension; Echo Doppler study

Hypertensive cardiac disease shows early alteration of left ventricular diastolic filling, characterized by a longer isovolumetric relaxation period and by an altered E/A ratio on the mitral spectral Doppler. We chose ten hypertensive patients who had left ventricular hypertrophy, but no left ventricular dilatation or mitral valve insufficiency and had a good left ventricular shortening fraction (greater than 26%). After the washout period we studied each of the above-mentioned parameters before and after the acute administration of nifedipine, dinitrate isosorbide, and captopril. While captopril and dinitrate isosorbide induced a prolongation of the isovolumic relaxation time and an impairment of the E/A ratio in mitral spectral Doppler (i.e., left ventricular filling), nifedipine induced an improvement in both parameters. The three drugs also induced a similar reduction in systemic blood pressure values (i.e., similar afterload). We therefore suggest that changes in diastolic function in hypertrophied cardiac fibers, induced by nifedipine, may be the result of a double action: one mediated by hemodynamic changes, the other directly affecting the cellular calcium ion exchange.

Development of tolerance to nifedipine in patients with stable angina pectoris.

1. The possibility of development of tolerance to the anti-ischaemic and anti-anginal effects of nifedipine during sustained administration for 2 months was studied in 15 patients with stable angina pectoris by means of repeated exercise tests on a treadmill. 2. After acute administration of nifedipine (20-30 mg) substantial anti-ischaemic and anti-anginal effects lasted for at least 4 h in all patients. 3. During sustained nifedipine treatment with a dose schedule which provided continuous anti-ischaemic effect during a day (mean daily dose 82.7 +/- 6.0 mg, range 60-120 mg) a substantial attenuation of this effect was registered. The duration of the anti-ischaemic effect was 5.4 +/- 0.3 h after acute administration, decreasing significantly to 3.6 +/- 0.4 h during sustained administration. 4. The attenuation of the nifedipine effect was not associated with worsening of the patients' condition. 5. Plasma concentrations of nifedipine and its metabolite were similar after acute administration and during sustained treatment. Protein binding of nifedipine also remained constant during the study. 6. There was marked interindividual variation in the degree of attenuation of the nifedipine effect during sustained administration. In five patients nearly complete loss of nifedipine efficacy was registered. Eight to ten days after stopping regular administration of nifedipine only partial restoration of nifedipine effect was observed. 7. We conclude that during sustained nifedipine administration tolerance to its anti-ischaemic, anti-anginal and circulatory effects develops in a substantial number of patients with stable angina pectoris.

Elicitation of Myocardial Ischemia by Nifedipine in a Case of Coronary Artery Fistula

A 63-year-old woman had chest pain that worsened when nifedipine was given. She was found to have a right coronary-to-thorax angioma/fistula. Acute nifedipine administration elicited precordial symptoms, associated with ischemic changes in the inferior ECG leads and an obvious vasodilatation of the fistulous tract, suggesting that a nifedipine-induced "steal" phenomenon might be responsible for the paradoxic clinical response.

Long-term treatment of chronic obstructive lung disease by Nifedipine: an 18-month haemodynamic study

This long-term controlled study was undertaken to assess the haemodynamic effects of chronic administration of Nifedipine (N). Twenty patients suffering from pulmonary hypertension secondary to chronic obstructive lung disease were divided into two groups. One group (treatment group) was instructed to take 30 mg of N daily and the other (control group) did not take N. Haemodynamic measurements were recorded before and after an 18-month observation period. For patients in the treatment group, Nifedipine was stopped 24 h prior to the second investigation. Acute response to a single dose of Nifedipine (10 mg sublingually) was also evaluated in all patients during the first and second investigations in order to estimate a possible tachyphylaxis. No significant modification in heart rate, mean pulmonary pressure, mean arterial pressure or blood gases was observed. Conversely, a 10% decrease in cardiac output (p less than 0.05) occurred in the control group. Pulmonary vascular response to acute administration of Nifedipine was the same in both groups before and after the observation period. These results suggest that while long-term administration of Nifedipine to patients with chronic obstructive lung disease does not improve pulmonary pressure, it may prevent a decrease in cardiac output. No tachyphylaxis was noted.

Natriuretic Effect of Acute Nifedipine Administration Is Not Mediated by the Renal Kallikrein-Kinin System

Despite their vasodilating action, calcium antagonists increase renal sodium excretion. To ascertain whether renal kallikrein plays a role in the renal effects of calcium antagonists, nifedipine (N) (10 mg orally) or placebo (P) was given to 17 male patients with mild to moderate essential hypertension during a 6-h infusion of either saline (S) or aprotinin (A) (2 X 10(6) KIU in 200 ml of saline). Blood pressure (BP) and heart rate (HR) were measured every 10 min, and blood samples were taken at -10, 0, 30, 60, 120, 240, 360 min for plasma renin activity (PRA), creatinine, and osmolarity determinations. Urinary kallikrein, aldosterone, creatinine, and electrolytes were measured in 6-h urine collections. The acute administration of N induced a significant systolic BP (SBP) and diastolic (DBP) fall and a transient PRA increase that peaked at 30 min and were not modified by A infusion. Urinary volume (+47%), Na+ (+54%) and Cl- (+58%) excretion were significantly enhanced by N. There were less pronounced and statistically not significant increases in urinary excretion of Ca2+ (+38%) and K+ (+29%). Infusion of A did not interfere with the natriuretic effect of N. Our data do not support the hypothesis that the kallikrein-kinin system plays an important role in mediating the renal effects of nifedipine in humans.

Pharmacokinetics and pharmacodynamics of nifedipine in patients at steady state.

The pharmacokinetics and associated pharmacodynamics of nifedipine were studied at steady state in 12 patients with angina pectoris who were receiving nifedipine 10-40 mg tid. After dosing, serum nifedipine concentrations rose rapidly and decayed in a log-linear fashion. The mean (+/- SEM) maximum serum concentration (Cmax) after dose normalization, and the time to Cmax (tmax) were 115 +/- 7 ng/mL and 0.72 +/- 0.13 hr, respectively. The mean area under the plasma concentration-time curve per 10-mg dose was 304 +/- 34 hr-ng/mL. The average elimination rate constant was 0.205 +/- 0.016 hr, and the harmonic mean elimination half-life was 3.4 hr (range, 2.5-4.9 hr). Heart rate increased (5-6 beats/min, P less than .05) from baseline for up to one hour after dose, while mean diastolic blood pressure decreased (6-15 mm Hg, P less than .05) for up to four hours. Cardiac output was increased (1.1-2.8 L/min, P less than .05), and calculated total systemic resistance (3.8-6.3 mm Hg/L/min, P less than .05) was decreased for the entire dosing interval after nifedipine dosing. Hysteresis plots for heart rate and mean diastolic blood pressure showed a time lag between changes in serum nifedipine concentrations and heart rate, but not between serum nifedipine concentrations and blood pressure. Changes in cardiac output did not correlate with serum nifedipine concentrations. The steady-state kinetic and dynamic parameter values in patients with angina pectoris in this study were similar to those found in healthy volunteers or hypertensive patients after acute nifedipine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

The response of the coronary collateral circulation to acute administration of nifedipine: an angiographic and ergometric study

To evaluate the role of collaterals in patients with effort angina we retrospectively compared the coronary cineangiograms of 14 subjects (“responders”) who improved their exercise tolerance after acute nifedipine therapy with 14 subjects (“non-responders”) with the same symptomatology who did not respond to the same treatment. The status of collaterals was graded with a score from a minimum of 0 to a maximum of 5. The responders showed a greater score than the non-responders (3 ± 1 vs. 1 ± 1, P < 0.001), whereas there was no difference in the number of stenosed vessels between the two groups (1.8 ± 0.9 vs. 2 ± 0.8). Thus, in patients with effort angina and critical coronary stenosis, the presence of an efficient coronary collateral circulation can favour the increase in coronary flow reserve after vasodilator therapy. Our results suggest that the grading of collaterals may add useful information to the simple classification of one-, two- or three-vessel coronary artery disease.

Nifedipine dilates the pulmonary vasculature without producing symptomatic systemic hypotension in upright resting and exercising patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease.

Vasodilator therapy may lower pulmonary vascular resistance in patients with chronic air-flow limitation. However, the effects of these agents on left ventricular afterload, cardiac output, and bronchial smooth muscle could lower the calculated pulmonary vascular resistance without specifically affecting pulmonary vascular tone. In addition, systemic hypotension in the upright position and worsening ventilation/perfusion heterogeneity could limit their use. We determined the pulmonary driving pressure (pulmonary arterial-pulmonary arterial wedge pressure) to flow relationship, as well as the transmural pulmonary arterial pressure in 9 patients with severe chronic air-flow limitation with pulmonary hypertension while in a clinically stable condition. Measurements were made at rest and during 3 stages of progressively increasing upright exercise on a bicycle before and after a single 20-mg dose of nifedipine. Nifedipine displaced both the driving pressure to flow and the pulmonary arterial transmural pressure to flow relationships towards higher flows in every subject, suggesting an active vasodilation. In the upright position, PaO2 did not change, and the systemic arterial pressure was only mildly reduced. In patients with pulmonary hypertension from chronic air-flow limitation, acute administration of nifedipine to upright patients causes pulmonary, as well as systemic vasodilation without causing symptomatic hypotension or reducing arterial oxygenation.

Noninvasive assessment of acute effects of nifedipine on rest and exercise hemodynamics and cardiac function in patients with aortic regurgitation

The acute effects of nifedipine (20 mg sublingually) on hemodynamics and cardiac function were studied at rest and during supine bicycle exercise in 20 patients with aortic regurgitation. At rest, heart rate increased by 13%, systemic vascular resistance decreased by 34% and regurgitant index decreased by 17%. The change in systemic vascular resistance was related to its initial rest level (r = 0.82, p less than 0.001) and to the changes in forward cardiac output (r = 0.58, p less than 0.01) and regurgitant index (r = 0.60, p less than 0.01). Left ventricular end-diastolic and end-systolic volumes, stroke volume and ejection fraction were unchanged, whereas right ventricular ejection fraction increased. During exercise, nifedipine administration further increased heart rate by 8% and decreased systemic vascular resistance by 19%. Both forward stroke volume and forward cardiac output increased, but total left ventricular stroke volume was unchanged, resulting in a significant decrease in regurgitant index. Although left ventricular end-diastolic volume was slightly decreased, end-systolic volume did not increase; thus, ejection fraction was higher than that during control exercise (p less than 0.01). Right ventricular ejection fraction increased further. In aortic regurgitation, the acute administration of nifedipine improved cardiac performance and reduced regurgitation at rest and during exercise as a result of afterload reduction and increased heart rate. Whether these beneficial effects will occur during long-term therapy requires further investigation.