Exaggerated natriuresis as a candidate intermediate phenotype in spontaneously hypertensive rats

OBJECTIVE: To determine whether exaggerated natriuresis and exaggerated renal sympathoinhibition during volume loading constitute an intermediate phenotype in spontaneously hypertensive rats. DESIGN: The borderline hypertensive rat, the F1 of a cross between a spontaneously hypertensive rat and a normotensive Wistar-Kyoto rat, is a NaCl-sensitive model of genetic hypertension. In addition to hypertension, borderline hypertensive rats fed 8% NaCl food develop characteristic alterations in regulation of renal sympathetic nerve activity and neural regulation of renal function similar to those in the spontaneously hypertensive rat parent. Like the Wistar-Kyoto rat parent, borderline hypertensive rats fed 1% NaCl food remain normotensive and do not exhibit these alterations in renal sympathetic neural mechanisms. These renal sympathetic neural mechanisms constitute a complex quantitative trait that could represent an intermediate phenotype. METHODS: A backcross population, developed by mating borderline hypertensive rats with Wistar-Kyoto rats, was fed 8% NaCl food for 12 weeks from age 4 to 16 weeks. Responses to intravenous isotonic saline volume loading (10% body weight/30 min) in 81 backcross rats chronically instrumented for measurement of mean arterial pressure, renal sympathetic nerve activity, and urinary sodium excretion were determined. RESULTS: Mean arterial pressure was 105-180 mmHg and was not correlated to the magnitude either of the decrease in renal sympathetic nerve activity or of the increase in urinary sodium excretion during volume loading. CONCLUSIONS: These two aspects of the complex quantitative trait, exaggerated natriuresis and exaggerated renal sympathoinhibition during volume loading, are not part of an intermediate phenotype in spontaneously hypertensive rats.