Spontaneously Hypertensive Rat Y Chromosome Increases Indexes of Sympathetic Nervous System Activity

Abstract

Previous studies from our laboratory have demonstrated that the Y chromosome from the spontaneously hypertensive rat (SHR) is responsible for a significant portion of the elevated blood pressure and also produces an earlier pubertal rise in plasma testosterone. We performed the following studies to determine whether the SHR Y chromosome raises blood pressure by sympathetic nervous system responses as measured by adrenal chromogranin A and plasma and tissue catecholamines. Male SHR from the University of Akron colony were studied from 5 to 20 weeks of age. Blood pressure was measured by tail-cuff, tail artery cannulation, and aortic telemetry (Data Sciences); acute (air stress) and chronic (territorial colony) social stressors were compared; blood was collected for determination of plasma catecholamines; and adrenal glands were analyzed at 15 weeks for catecholamines. Rats with the SHR Y chromosome had higher blood pressure and plasma norepinephrine than those with the normotensive Wistar-Kyoto (WKY) Y chromosome. However, the SHR Y chromosome did not significantly change responsiveness to acute or chronic stressors. Phentolamine and clonidine prevented the stress responses. Adrenal chromogranin A levels were elevated 37% and 40% and adrenal norepinephrine content 29% and 100% at 4 and 10 weeks of age, respectively, in rats with an SHR Y chromosome compared with WKY. Chemical sympathectomy normalized blood pressure in all strains and significantly reduced norepinephrine (36% to 41%) in all strains except in WKY, which already had a normal blood pressure. In conclusion, the SHR Y chromosome appears to increase the chronic sympathetic nervous system. A potential mechanism could be a Y locus that influences chronic sympathetic nervous system activity, which may reinforce neurohumoral factors and structural components of the vessel wall, accelerating the development of hypertension.

Effects of the Y Chromosome on Cardiovascular Risk Factors in Japanese Men

“…Results based on the chromosome Y consomic strains derived from SHR and WKY rats have suggested the possible effect of Y chromosome on determination of BP (8)(9)(10)(11). It can be speculated that sexual dimorphism in cardiovascular risk can be partly explained by the effect of the Y chromosome, and polymorphisms within the male specific non-recombining region of the Y chromosome are linked to increased cardiovascular risk in men.…”

“…Analyses of the Y chromosome consomic strains derived from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) revealed the possible effect of the Y chromosome on determination of blood pressure (BP), with an SHR Y chromosome in a WKY genetic background exerting the BP-elevating effect (8)(9)(10). Similarly, replacement of the SHR Y chromosome with that of Brown Norway rats has been associated with significant reduction in both SBP and DBP (11).…”

A hypertensive father, but not hypertensive mother, determines blood pressure in normotensive male offspring through body mass index

“…More interestingly, higher levels of BP in the offspring of hypertensive parents are often associated with an increase in plasma insulin concentrations or a decrease in insulin sensitivity and increased response of adrenergic nervous system to mental stress. [9][10][11]14,15 In fact, Scherrer et al 16 have demonstrated the relationship between BMI and the rate of sympathetic nerve discharge to skeletal muscle vasculature in normotensive subjects. In this context, we have demonstrated in our previous study that BP levels are well correlated to BMI in non-obese, normotensive freshman students having both hypertensive parents, and that such offspring have relatively higher plasma insulin concentrations.…”

“…Ely et al [9][10][11] have reported that Y chromosome independently elevates BP in male SHR probably through increased sympathetic nervous activity. The enhanced adrenergic nerve activity influences both BP values and glucose metabolism.…”

α1‐Adrenoceptor activation of PKC‐ε causes heterologous desensitization of thromboxane receptors in the aorta of spontaneously hypertensive rats

“…α 1-adrenoceptors, especially the α1D subtype, play an important role in the homeostatic control of vascular tone, and are involved in sympathetic regulation of arterial BP (Civantos Calzada and Aleixandre de Artinano, 2001;Tanoue et al, 2002). The sympathetic nervous system is hyperactive in the SHR (Head et al, 1985;Scott and Galway, 1985;Mangiarua and Lee, 1990;Ely et al, 1997). Thus, the interaction observed in the present study between the downstream effects of α1-adrenoceptor activation and the response to PGE2 may play a modulating role in reducing prostanoidinduced vasoconstriction in the SHR, in which such responses are prominent (Lüscher and Vanhoutte, 1986;Tang et al, 2005;Tang and Vanhoutte, 2008).…”