SUMMARY 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 a,-adrenergic agonist methoxamine (i.e., higher ED.*). SHR had hi 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 a,-adrenergic receptor agonist was lower in SHR. The a 2 -adrenergic receptor antagonist rauwolscine attenuated the pressor response to electrical stimulation in SHR and WKY but increased it in Sprague-Dawley rats. The a r 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 a r adrenergic receptors in SHR compensates partially for increased sympathetic activity or hyperinnervation, or both. (Hypertension 11: 427-432, 1988) KEY WORDS • spontaneously hypertensive rats • normotensive rat strains • sympathetic nervous system * adrenergic receptors * vasoconstrictor mechanisms H ISTORICALLY, the normotensive control for spontaneously hypertensive rats (SHR) has been the Wistar-Kyoto rat (WKY) strain from which it was derived. Comparisons of SHR and WKY implicate elevated sympathetic nerve activity, sympathetic hyperinnervation, and enhanced vascular reactivity to norepinephrine in the development and maintenance of hypertension.
"4 However, it is not known whether these differences distinguish SHR from other normotensive strains with different genetic backgrounds. Further, for these perturbations to raise blood pressure, it would seem that compensatory mechanisms (e.g., desensitization of adrenergic receptor-mediated vasoconstriction and prejunctional Received June 1, 1987; accepted December 16, 1987. adrenergic receptor-mediated inhibition of norepinephrine release) must also be deficient or obtunded. The possibility of identifying mechanisms linked causally to hypertension in SHR is aided by comparison with normotensive strains of different genetic backgrounds. 56 Accordingly, in the present experiment...
Post--not prenatal maternal stress disrupts BP and HR control in rat offspring; disruption is greater after restraint than injection. There is sympathetic hyperactivity in preweanlings and hypoactivity in adults.
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