Renal vascular reactivity to P(2)-purinoceptor activation in spontaneously hypertensive rats.
This study was performed to determine the possible contribution of an imbalance between P(2X) (vasoconstriction) and P(2Y) (vasodilation)-purinergic reactivity to the increased vascular resistance of spontaneously hypertensive rats (SHR). The vasoactive responses to alpha,beta-methylene ATP and 2-methylthio ATP specific agonists, respectively, for P(2X) and P(2Y) purinergic receptors were characterized in isolated perfused kidneys from Wistar Kyoto (WKY) and SHR. To analyze P(2X)- and P(2Y)-purinergic reactivity we used phenylephrine and barium chloride, or acethylcholine (ACh) and sodium nitroprusside (NP) as reference compounds, respectively. The renal vasculature from SHR showed markedly enhanced reactivity to alpha,beta-methylene ATP, phenylephrine and barium chloride. The dose-response curves were characterized by a similar threshold, with a greater maximal response. There were no significant differences in the dose-response curves or in maximal vasodilation to 2-methylthio ATP, ACh or NP when both groups were compared, except at the dose of 10(-6) g/g kidney weight of NP in which the SHR group showed an increased responsiveness. The results indicate that the increased responsiveness of kidneys from SHR to alpha,beta-methylene ATP may be due to nonspecific functional changes in the renal vasculature rather than to a specific alteration in the activity of renal P(2X)-purinoceptors. Our results also indicate that P(2Y)-purinergic reactivity, nitric oxide-induced vasodilation and the cGMP-dependent mechanisms of vasodilation are well preserved in SHR.
Fernández
O
O
Departamento de Fisiología, Facultad de Medicina, Unidad de Nefrología Experimental, Hospital Virgen de las Nieves, Granada, Spain.
Wangensteen
R
R
Osuna
A
A
Vargas
F
F
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D058910:Purinergic P2 Receptor Agonists; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D013873:Thionucleotides; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; C008501:2-methylthio-ATP