Exaggerated natriuresis as a candidate intermediate phenotype in spontaneously hypertensive rats

To determine whether exaggerated natriuresis and exaggerated renal sympathoinhibition during volume loading constitute an intermediate phenotype in spontaneously hypertensive rats.

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.

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.

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.

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.