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

Abstract

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. 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. 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. 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. Normalized ED50 values (ED50 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. 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. 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 alpha-adrenoceptors are dominant, potentiation of the vasoconstrictor effect ofendogenous catecholamines by Bay K 8644 seems to contribute to its vasoconstrictor effect.