Mechanism of the pressor effect of the calcium agonist, BAY k 8644, in the intact rat.
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 micrograms/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 micrograms/kg/h) blocked 62-84% of the pressor response of BAY k 8644 (p less than 0.001 from control responses). The alpha-adrenergic receptor antagonist phentolamine (400 micrograms/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.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002395:Catecholamines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015737:Nisoldipine; D009568:Nitrendipine; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012504:Saralasin / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology
D000098:Acetophenones; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002395:Catecholamines; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D013777:Tetrazoles; D001127:Arginine Vasopressin; D015737:Nisoldipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C044660:LY 171883; C045749:SQ 29548; D009568:Nitrendipine; D012504:Saralasin; D009543:Nifedipine; D009638:Norepinephrine; D010646:Phentolamine