Nisoldipine inhibits vasoconstrictor responses in the cat pulmonary vascular bed.
The influence of nisoldipine, a dihydropyridine calcium entry antagonist, on vascular resistance and vasoconstrictor responses was investigated in the feline pulmonary vascular bed under conditions of controlled blood flow. The calcium channel blocking agent caused a small reduction in lobar vascular resistance and blocked pulmonary vasoconstrictor responses to BAY K 8644, an agent which promotes calcium entry. The calcium entry blocking agent also reduced pulmonary vasoconstrictor responses to methoxamine and to BHT 933, alpha 1- and alpha 2-adrenoceptor agonists, and to U 46619, an agent which mimics the actions of thromboxane A2. Although there was a marked difference in vasoconstrictor potency in the pulmonary vascular bed, responses to the thromboxane mimic and to the alpha 1- and alpha 2-adrenoceptor agonists were reduced by approximately the same extent. The increases in systemic arterial pressure in response to BAY K 8644, methoxamine, and BHT 933 were also reduced by nisoldipine, and the calcium entry antagonist reduced systemic arterial pressure and systemic vascular resistance. The results of the present study suggest that an extracellular source of calcium is required for the maintenance of vascular tone and for the expression of vasoconstrictor responses, resulting from activation of alpha 1- and postjunctional alpha 2-adrenoceptors and thromboxane receptors in the feline pulmonary vascular bed.
Kadowitz
P J
PJ
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Lippton
H L
HL
Bellan
J A
JA
Hyman
A L
AL
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002415:Cats; D005260:Female; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015737:Nisoldipine; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D002121:Calcium Channel Blockers; D011450:Prostaglandin Endoperoxides, Synthetic; D014665:Vasodilator Agents; D015737:Nisoldipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C015603:azepexole; D008729:Methoxamine; D009543:Nifedipine