Similarity and dissimilarity of the vasoconstrictor effects of Bay K 8644 on coronary, femoral, mesenteric and renal circulations of dogs

Abstract

1 The effect of the dihydropyridine calcium agonist Bay K 8644 on the coronary, femoral, mesenteric and renal circulations was investigated and compared with that of noradrenaline in pentobarbitone-anaesthetized dogs.2 The left anterior descending coronary, femoral, cranial mesenteric and renal arteries were cannulated and their arterial beds perfused with autologous blood at a constant pressure slightly higher than the mean systemic arterial blood pressure. Bay K 8644 (0.1-300 nmol) and noradrenaline (0.1-300 nmol) were injected intra-arterially. 3 Bay K 8644 decreased blood flow (vasoconstriction) in all 4 arterial beds. A maximum decrease was attained at 100 nmol and a further increase.in dose did not appear to result in a further decrease in blood flow. 4 At maximum effects blood flow decreased to about 35% of the basal value in coronary, 30% in femoral, 20% in renal and 15% in mesenteric circulation.5 Normalized ED50 values (ED_% divided by basal flow) of Bay K 8644 were 0.07 ± 0.02 nmol in the femoral, 0.08 ± 0.01 nmol in the coronary, 0.16 ± 0.06 nmol in the mesenteric and 0.55 ± 0.19 nmol in the renal circulation. 6 At 100 nmol, the values for the half-duration of Bay K 8644 vasoconstrictor effects were about 196 s in the renal, 78 s in the mesenteric, 84 s in the femoral and 21 s in the coronary circulation. 7 Noradrenaline produced a dose-dependent decrease in blood flow in femoral, mesenteric and renal circulations, and was about 2 times in femoral, 4 times in mesenteric and 9 times in renal circulation more potent than Bay K 8644.8 Bay K 8644 produced slight increases in the maximum rate of rise of left ventricular pressure and intraluminal pressure of the ileum. However, the increases did not appear to impede blood flow. 9 Bay K 8644 produced slightly but significantly greater femoral vasoconstriction in normal dogs than in reserpine-pretreated dogs. 10 From these results it was concluded that differences in potency, effectiveness and duration of the vasoconstrictor effects of Bay K 8644 between the 4 arterial beds probably derive from differences in characteristics ofthe smooth muscle ofresistance vessels there. In arterial beds where x-adrenoceptors are dominant, potentiation of the vasoconstrictor effect ofendogenous catecholamines by Bay K 8644 seems to contribute to its vasoconstrictor effect.

Role of potassium channels in coronary vasodilation

“…27–30 Conversely, Bay K 8644, a dihydropyridine with agonist rather than antagonist properties, elicits coronary vasoconstriction. 31 The coronary vasodilator effects of L-type Ca 2+ channel blockers are rather simple to understand; these drugs directly inhibit a major Ca 2+ entry pathway in CASMC and thus reduce the intracellular Ca 2+ required to maintain contraction. The vasodilatory effects of K + channel openers are similar; however, their mechanism involves an additional step to hyperpolarize E m .…”

Ion Channel Modulators as Potential Positive Inotropic Compounds for Treatment of Heart Failure

“…Thus, Caz+ channel activators produce vasoconstriction in vivo at doses causing minimal to significant positive inotropic responses preventing an increase in cardiac output (Preuss et al 1984;Hom et al 1992). Further, there is no selectivity between vascular beds for Bay K 8644 (Ishii et al 1986). The dihydropyridine calcium channel antagonists show selectivity for vascular rather than myocardial tissue.…”

Differential antagonism by Bay K 8644 of vasodilator effects of nifedipine, diltiazem, nicorandil and nitroglycerin in dog femoral circulation

“…Bay K 8644, a dihydropyridine calcium agonist, increases the systemic arterial blood pressure when administered intravenously (i.v.) to dogs (Schramm et al, 1983a,b) and decreases blood flow through the coronary (Wada et al, 1985;Ishii et al, 1986), femoral, mesenteric (Ishii et al, 1986) and renal (Ishii et al, 1986;Ogawa & Ono, 1986) arterial beds (i.e. resistance vessels) in dogs when administered intraarterially (i.a.).…”