Tachyphylaxis to 5-hydroxytryptamine in perfused kidneys from spontaneously hypertensive and normotensive rats.
Isolated perfused kidneys from 4- to 6-month-old spontaneously hypertensive rats (SHR, Japanese strain) exhibit increased "vascular reactivity" to 5-hydroxytryptamine (5-HT) and a slower rate of development of tachyphylaxis to this substance when compared with kidneys from normotensive Wistar-Kyoto (WKY) rats. We investigated the possibility that the reduced rate of development of tachyphylaxis could be related to a interaction of 5-HT with adrenergic mechanisms or with endogenous 5-HT. Tachyphylaxis was induced by repeated administration of 5-HT to kidneys from SHR and WKY rats. This procedure did not affect vasoconstrictor responses evoked by norepinephrine. The development of tachypylaxis to 5-HT in kidneys from SHR and WKY rats was not changed by chemical sympathectomy with 6-hydroxydopamine. Treatment of SHR with para-chlorophenylalanine did not affect their blood pressure or the development of tachyphylaxis to 5-HT. These results indicate that delayed tachyphylaxis to 5-HT in kidneys of SHR is not due to an interference with adrenergic mechanisms and does not depend on endogenous 5-HT levels. The phenomenon represents an unusual modification of vascular smooth muscle exposed to chronic high pressure, but it is unlikely that the vasoconstrictor effects of 5-HT contribute to the maintenance of hypertension in the SHR.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology; D013618:Tachyphylaxis
D011942:Receptors, Adrenergic, alpha; D012701:Serotonin; D010134:Fenclonine; D009638:Norepinephrine