Reversal of endothelin-1-induced ocular hemodynamic effects by low-dose nifedipine in humans.

BACKGROUND AND PURPOSE: There is evidence that calcium channel blockers may be useful in patients with normal tension glaucoma and vasospastic reactions. We therefore hypothesized that calcium channel blockers may increase ocular blood flow and that there may be a functional antagonism between endothelin-1 (ET-1) and calcium channel blockers in the ocular vasculature. METHODS: This was a randomized, double-blind, three-way crossover study with respect to ET-1 infusions (placebo, 2 ng/kg/min ET-1, and 4 ng/kg/min ET-1) and a randomized double-blind study in two parallel groups with respect to nifedipine (placebo or 5 mg nifedipine). Ocular hemodynamics in the 12 healthy subjects participating in the study was assessed by laser interferometric measurement of fundus pulsation amplitude (FPA) in the optic disc and two-dimensional scanning laser Doppler flowmetry in the optic disc. RESULTS: ET-1 caused a dose-dependent decrease in FPA and flow. With a dose of 4 ng/kg/min a decrease of -18% +/- 5% (p < 0.001) and -17% +/- 5% (p = 0.023) on FPA and flow, respectively, were observed. This effect was completely reversed by nifedipine compared with placebo (FPA, p < 0.001; flow, p = 0.011). However, nifedipine did not affect ocular hemodynamics after placebo infusion. CONCLUSIONS: These results show that nifedipine does not increase optic nerve head blood flow during baseline conditions but reverses ET-1-induced constriction in ocular vasculature at doses that do not affect systemic hemodynamics. This supports the close relation of the therapeutic effect of calcium channel blockers in patients with normal tension glaucoma to the endothelin system. Moreover, the present study provides a strong rationale for a study of low dose nifedipine as a supplementary medication in glaucoma patients.

Influence of acetylsalicylic acid on acute circulatory effects of the beta-blocking agents pindolol and propranolol in humans.

In ten hospitalized, hypertensive male patients (WHO stage I or II) an acetylsalicylic acid (ASA) pretreatment (p.o. 5.0 g/24 h) prevented the acute blood pressure (BP) lowering effect of pindolol (1 mg i.v.) as compared with a placebo pretreatment. Similarly in six other hospitalized male patients (four normotensive, two slightly hypertensive) a single dose of ASA (1.0 or 1.5 g orally), which alone tended to raise the BP, reduced the decrease in systolic BP and led to an increase in diastolic BP following propranolol (5 mg i.v.). The ASA pretreatment did not affect the decrease in heart rate and cardiac contractility (measured by systolic time intervals) after the application of pindolol and propranolol, respectively. In conformity with data in the literature, the results suggest a possible connection between endogenous prostaglandins and the hypotensive, but not negative chronotropic and inotropic activity of the beta-blocking agents investigated.

Comparative study of the cardiac and peripheral vascular effects of strophantin K and lanatoside C in coronary heart disease.

The effects of intravenous strophanthin K (0.125 and 0.25 MG) and lanatoside C (0.4, 0.8 and 1.6 mg) on systolic time intervals (STI) and impedance plethysmographic (IP)P values were studied in ten patients with compensated coronary heart disease. The heart rate decreased significantly during a two-hour study in the lying position after both glycosides and placebo; the systemic blood pressure remained unchanged. Electromechanical systole (QS2), left ventricular ejection time (LVET) and preejection period (PEP), corrected for heart rate (QS2I, LVETI, PEPI), showed no change after placebo. The glycosides caused no change in LVETI. QS2I was significantly shortened only after lanatoside C 1.6 mg. PEPI and ICT were significantly shortened by both doses of strophanthin K and lanatoside C; the effects were dose-related. Taking into consideration the effects of cardiac glycosides on STI, use of the index ICT/QS1, the quotient of isovolumic contraction time and electro-mechanical delay, is proposed, because it showed quite sensitively the increase in myocardial contractility after digitalis. The effect of strophanthin K could be detected 10 minutes, and that of lanatoside C 30-40 minutes, after injection. The amplitude of the IP curve and the relative pulse volume showed positive and negative changes without any trend after administration of placebo or glycoside. The data suggests that the usual therapeutic doses of these cardiac glycosides do not cause significant changes in the peripheral circulation in patients with compensated coronary heart disease, but their action on STI is quite marked, showing a positive inotropic effect.