Basal nitric oxide production is impaired in offspring of patients with essential hypertension

There is considerable evidence that endothelium-dependent nitric oxide (NO)-mediated vasodilatation in response to acetylcholine is impaired in essential hypertension, whereas the endothelium-independent response to sodium nitroprusside is normal. More limited data have suggested that there is also reduced vasoconstriction in response to N(G)-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of basal NO release. As it is not known whether endothelial dysfunction in hypertension, if indeed present, is a cause or consequence of the condition, we have studied the normotensive offspring of parents with essential hypertension. Both basal and stimulated vascular responses were examined in 12 normotensive offspring [mean age (+/-S.E.M.) 26.1+/-1.4 years] of parents with essential hypertension and compared with those in 12 age-matched offspring (mean age 25.6+/-1.1 years) of normotensive subjects. Forearm blood flow was measured simultaneously in both arms by venous occlusion plethysmography, both at baseline and during intra-arterial brachial infusion of increasing doses of acetylcholine, sodium nitroprusside, noradrenaline and L-NMMA. There were no significant differences between the groups in the responses to acetylcholine, sodium nitroprusside or noradrenaline. In contrast, the vasoconstrictor response to L-NMMA was significantly blunted in the offspring of hypertensive parents compared with that in the offspring of normotensive parents (P=0.005). Thus endothelial dysfunction, as demonstrated by impaired basal production of NO, is present in subjects at high risk of essential hypertension, and does not occur simply as a consequence of the condition.