Pressor mechanisms linked obligatorily to spontaneous hypertension in the rat.
To identify genetic factors linked obligatorily to hypertension in the rat, pithed spontaneously hypertensive rats (SHR) were compared with genetically similar (Wistar-Kyoto rats; WKY) and different (Sprague-Dawley) normotensive strains. The only variables that distinguished SHR from both WKY and Sprague-Dawley rats were a greater maximum pressor response to electrical stimulation of sympathetic outflow and decreased sensitivity to submaximal doses of the alpha 1-adrenergic agonist methoxamine (i.e., higher ED50). SHR had in common with Sprague-Dawley rats basal blood pressure after pithing plus adrenalectomy and the maximum pressor response to methoxamine; both these values were higher than those in WKY. All strains demonstrated equal sensitivity of the vasoconstrictor response to endogenous norepinephrine released by electrical simulation at submaximal frequency, even though sensitivity to the alpha 1-adrenergic receptor agonist was lower in SHR. The alpha 2-adrenergic receptor antagonist rauwolscine attenuated the pressor response to electrical stimulation in SHR and WKY but increased it in Sprague-Dawley rats. The alpha 1-adrenergic receptor antagonist prazosin attenuated the response more in SHR and WKY than in Sprague-Dawley rats. We conclude that 1) sympathetic hyperactivity is linked obligatorily to hypertension in SHR; 2) increased basal blood pressure and noradrenergic vasoconstrictor response are present in SHR, but they are not obligatorily linked to hypertension; 3) feedback inhibition of norepinephrine release is comparable in SHR or WKY and poorly developed compared with that in Sprague-Dawley rats; 4) decreased sensitivity of the pressor response to stimulation of vascular alpha 1-adrenergic receptors in SHR compensates partially for increased sympathetic activity or hyperinnervation, or both.
Mills
E
E
Department of Pharmacology, Duke University Medical School, Durham, North Carolina.
Bruckert
J W
JW
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004558:Electric Stimulation; D005260:Female; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000502:physiology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D013564:Sympathetic Nervous System / Q000503:physiopathology; D015016:Yohimbine / Q000494:pharmacology
D015016:Yohimbine; D008729:Methoxamine; D009638:Norepinephrine; D011224:Prazosin