Yohimbine-induced alterations in alpha(2)-adrenoceptors in kidney regions of the spontaneously hypertensive rats: an autoradiographic analysis.
We have tested the hypothesis that a pharmacologically determined alteration in renal alpha(2)-adrenoceptor (alpha(2)-AR) density might be a pathophysiologically important factor of genetic hypertension in the spontaneously hypertensive rats (SHRs). First, we compared he regional distribution and biochemical parameters of alpha(2)-ARs in SHRs and Wistar-Kyoto (WKY) rats, using the full agonist [(3)H]UK 14304. Secondly, we evaluated the effect of selective blockade and stimulation of alpha(2)-ARs on the development of hypertension and on renal alpha(2)-AR density and regional distribution in SHRs. [(3)H]UK 14304 binding was distributed predominantly over the outer medulla, less abundantly over the inner medulla and was almost absent from the renal cortex. Renal alpha(2)-ARs were found to be increased in SHRs at the ages tested compared with their respective controls and the increase was completely localized to the outer medulla. In these rats, blood pressures immediately before sacrifice were significantly higher in the hypertensive group compared with normotensive controls. The daily administration of SK&F 86,466 or clonidine significantly decreased the blood pressure but the autoradiographic studies showed that the prolonged administration of yohimbine to rats for two weeks resulted in a large increase in the density of alpha(2)-ARs in some areas of the rat kidney but not in others. Taken together these data do not support the hypothesis that alteration in renal alpha(2)-ARs (as measured by autoradiography) is crucial for the maintenance of hypertension in the SHR model.
Sáiz
Jesús
J
Department of Pharmacology and Toxicology, Faculty of Medicine, University of Córdoba, Avenida Menéndez Pidal, s/n, 14071 Córdoba, Spain. ft1samaj@uco.es
Pazos
Angel
A
Del Olmo
Elena
E
Sáiz
Vanesa
V
Sánchez
Adela
A
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D000068438:Brimonidine Tartrate; D003000:Clonidine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D014316:Tritium; D015016:Yohimbine / Q000494:pharmacology*
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D001552:Benzazepines; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D014316:Tritium; D015016:Yohimbine; D000068438:Brimonidine Tartrate; D003000:Clonidine; C039139:benalfocin