Renal Sympathetic Neural Mechanisms as Intermediate Phenotype in Spontaneously Hypertensive Rats

Abstract

Abstract The borderline hypertensive rat, the F 1 of a cross between a hypertensive spontaneously hypertensive rat (SHR) and a normotensive Wistar-Kyoto (WKY) rat, is a NaCl-sensitive model of genetic hypertension. In addition to hypertension, borderline hypertensive rats fed 8% NaCl develop characteristic alterations in the regulation of efferent renal sympathetic nerve activity and the neural control of renal function that are similar to those observed in the SHR parent. Like the normotensive WKY rat parent, borderline hypertensive rats fed 1% NaCl remain normotensive and do not exhibit these alterations in renal sympathetic neural mechanisms. These renal sympathetic neural mechanisms constitute a complex quantitative trait that may represent an intermediate phenotype. They have a plausible pathogenetic role in hypertension and are different between SHR and WKY rats. This study evaluated two aspects of this complex quantitative trait, enhanced renal sympathoexcitation with air-jet stress and enhanced renal sympathoinhibition with guanabenz, as a candidate intermediate phenotype. As neither of these aspects was observed in two-kidney, one clip Goldblatt-hypertensive rats, this suggests that the trait is not secondary to hypertension from an acquired cause. In a backcross population (F 1 ×WKY) fed 8% NaCl for 12 weeks, both enhanced renal sympathoexcitation with air-jet stress and enhanced renal sympathoinhibition with guanabenz cosegregated with the hypertension. These results support renal sympathetic neural mechanisms as an intermediate phenotype in SHR.