Characterization of the alpha-1 adrenoceptors in the mesenteric vasculature from deoxycorticosterone-salt hypertensive rats: studies on vasoconstriction, radioligand binding and postreceptor events.
The vasoconstrictor responses to alpha-1 adrenoceptor agonists, binding behavior of alpha-1 adrenoceptors and postreceptor events in the mesenteric vasculature from deoxycorticosterone acetate-salt hypertensive rats were studied. The reactivity of perfused mesenteric artery to norepinephrine (NE) and phenylephrine, but not KCl, was enhanced significantly in the hypertensive rats compared with control rats. Prazosin antagonized the pressor response to NE more effectively in the hypertension than in the control. [3H]Prazosin binding was saturable and a single class of specific sites. Scatchard analysis revealed that the dissociation constant for [3H]prazosin was lower and the maximum binding capacity was greater in the hypertensive rats than in the control rats. The NE-stimulated phosphatidylinositol hydrolysis, estimated by measuring inositol 1,4,5-triphosphate (IP3) accumulation, was greater in the hypertensive rat artery compared with the control one. The IP3-induced contraction in the beta-escin-treated mesenteric large resistance vessel was smaller in the hypertensive rats. The vasoconstrictor response to phorbol 12,13-dibutyrate of the perfused mesenteric artery was larger in the hypertensive animals than in the control. Staurosporine antagonized the phorbol 12,13-dibutyrate-induced vasoconstriction in preparations from both rats. These results suggest that the increases in the number and affinity of alpha-1 adrenoceptors may result in an enhanced phosphatidylinositol hydrolysis accounting for an increased vascular reactivity to alpha-1 adrenoceptor agonists in deoxycorticosterone acetate-salt hypertensive rats. Furthermore, the enhancement of vasoconstrictor mechanism mediated by protein kinase C pathway may also contribute to vascular hyper-reactivity to NE, whereas the decreased IP3-induced contraction may function to minimize the hyper-reactivity observed in this model of experimental hypertension.
Suzuki
S
S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Takata
Y
Y
Kubota
S
S
Ozaki
S
S
Kato
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003900:Desoxycorticosterone / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D012965:Sodium Chloride / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D018340:Receptors, Adrenergic, alpha-1; D015240:Phorbol 12,13-Dibutyrate; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin