Heritable abnormalities of the renin-angiotensin-aldosterone system in essential hypertension

A subset of essential hypertensives sensitive to salt and having normal or high renin levels are termed nonmodulators. These subjects fail to modulate their renal blood flow and aldosterone responsiveness when dietary sodium is changed. We have found that a positive family history of hypertension in a first degree relative is exceedingly common in nonmodulators, suggesting that nonmodulation may be inherited. We have therefore begun a study in hypertensive sibships (two sibs in a family with essential hypertension under the age of 60 years), assessing the basal renal blood flow [p = aminohippurate (PAH) clearance] and the response of renal blood flow to infused angiotensin II (AII) (3 ng/kg/min) on a 200-mEq sodium intake. Nonmodulators fail to reduce their renal blood flow by at least 120 ml/min/1.73 m2 below control. We found that basal PAH clearance was significantly lower in nonmodulating versus modulating hypertensives on a high salt diet. Nonmodulation and basal PAH clearance were also found to significantly aggregate in families, and this was independent of sodium intake. Thus, these studies support the hypothesis that nonmodulation of renal blood flow in response to sodium loading is a heritable trait.