Mechanism of the pressor effect of the calcium agonist, BAY k 8644, in the intact rat¹

The purported calcium agonist BAY k 8644 was tested as a pressor agent in pentobarbital anesthetized and conscious Sprague-Dawley rats. A dose of 10 μg/kg increased mean arterial blood pressure (MABP) by 47 ± 3 mm Hg in anesthetized and 39 ± 3 mm Hg in conscious rats. The calcium channel blockers nitrendipine or nisoldipine (180 μg/kg/h) blocked 62-84% of the pressor response of BAY k 8644 (p < 0.001 from control responses). The α-adrenergic receptor antagonist phentolamine (400 μg/kg) failed to alter the Bay k 8644 induced pressor response either in the conscious or anesthetized state. Moreover, the thromboxane receptor antagonist, SQ-29,548 and the leukotriene D₄ and E₄ receptor antagonist LY-171,883 at doses that markedly block thromboxanes or leukotrienes, respectively, had no effect on the BAY k 8644 induced pressor response. Neither the angiotensin II receptor antagonist, saralasin nor an arginine vasopressin antagonist (AVP-A) modify the BAY k 8644 induced pressor response. Thus, BAY k 8644 appears to directly increase MABP in the rat by activation of calcium influx into vascular smooth muscle and/or cardiac muscle cells, probably without the action of any common secondary vasoconstrictor mediator.