Mechanisms of the enhanced contractile response to phenylephrine in thoracic aorta isolated from rats with dietary magnesium deficiency.
The mechanisms underlying the enhanced contractile response to phenylephrine (PE) and increased susceptibility to nifedipine of de-endothelialized thoracic aorta isolated from rats with dietary magnesium deficiency (Mg-deficient rats) were examined by functional and radioligand binding studies. Enhanced PE-induced contractions and increased susceptibility to nifedipine in Mg-deficient rats were not observed in the presence of 10 microM H7. PE significantly decreased the KD value without changing Bmax in the binding of [3H]PN200-110 to de-endothelialized aortic strips. The KD value obtained in the Mg-deficient rats was significantly smaller than that in the controls. Nifedipine displaced the binding of [3H]PN200-110 concentration-dependently, and the pKi value in Mg-deficient rats was significantly larger than that in the controls. A combination of PE and H7 abolished this difference. These results indicate that the modulation of L-type Ca2+ channels via the stimulation of alpha 1-adrenoceptors may be involved in the enhancement of vasoconstriction and increased susceptibility to nifedipine in aortas isolated from Mg-deficient rats. The H7-sensitive mechanisms may play an important role in these phenomena.
Sakaguchi
H
H
Department of Veterinary Pharmacology, Faculty of Agriculture, Kagoshima University, Japan.
Nishio
A
A
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D004032:Diet; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D017275:Isradipine / Q000378:metabolism; D008275:Magnesium Deficiency / Q000503:physiopathology*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*
D007546:Isoquinolines; D010879:Piperazines; D010656:Phenylephrine; D011189:Potassium Chloride; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D009543:Nifedipine; D017275:Isradipine