The dihydropyridine calcium channel blocker BAY t 7207 attenuates the exercise induced increase in plasma ANF and cyclic GMP in patients with mildly impaired left ventricular function

Abstract

In man, chronic antihypertensive calcium antagonist treatment improves cardiac function and reduces plasma ANF concentrations. Physical exercise increases cardiac workload and plasma ANF levels. In the present study, we investigated the effects of acute administration of the dihydropyridine calcium antagonist BAY t 7207 (BAY) during bicycle exercise on plasma ANF and plasma cyclic GMP levels, on mean arterial pressure (MAP), heart rate (HR), and on natriuresis and urinary urodilatin excretion. In a randomized, double-blind placebo controlled cross-over trial, 8 patients (age 56.8 +/- 2.5 y) with documented coronary artery disease and mildly impaired left ventricular function (EF 50.0 +/- 1.3%), received oral BAY (20 mg) or placebo. Forty-five minutes after medication, patients underwent a standardised exercise bicycle test in the supine position (6 min 25 W, 6 min 50 W). Before exercise, MAP was lower after BAY (88.8 +/- 4.1 mmHg) than after placebo (95.7 +/- 3.5 mmHg; p = 0.024), and HR was higher after BAY (76.8 +/- 3.5 bpm) than after placebo (69.5 +/- 3.6 bpm; p = 0.049). Plasma ANF tended to be higher after BAY (31.2 +/- 5.6 pg/ml) than after placebo (26.7 +/- 5.0 pg/ml), and plasma cGMP was not different (BAY 3.4 +/- 0.3, placebo 3.8 +/- 0.3 pmol/ml). During exercise, the relative increases in HR (+43%) and MAP (+17%) were identical after BAY and placebo. In contrast, ANF levels during exercise increased by 130 +/- 28% after placebo but only by 36 +/- 11% after BAY (p = 0.011). In parallel, plasma cyclic GMP increased by 61 +/- 13% after placebo and by 20 +/- 8% after BAY (p = 0.013). At the end of exercise, the BAY-induced reduction in plasma cyclic GMP reflected the reduction in diastolic arterial pressure (r = 0.717; p = 0.045). Compared to placebo, BAY treatment increased the fractional excretion rate of sodium from 0.46 +/- 0.11 to 0.90 +/- 0.22% (p = 0.016), without relation to urinary urodilatin excretion. Thus, the calcium antagonist BAY t 7207 attenuated the exercise-induced increase in plasma ANF and cyclic GMP probably due to its vasodilator effect. The relationship between blood pressure and the ANF system during exercise, which parallels findings during chronic antihypertensive treatment, may open a perspective for early evaluation of long-term therapy with calcium channel blockers.