Mechanism of lipid enhancement of α1-adrenoceptor pressor sensitivity in hypertension

Objective and design Plasma lipids enhance alpha 1-adrenoceptor pressor sensitivity, impair baroreflex function, and correlate with increased blood pressure. This clinical study was designed to determine whether the enhanced alpha(1)-pressor sensitivity induced by acute hyperlipidemia is primarily mediated by increased vascular alpha(1) responsiveness, reduced baroreflex sensitivity (BRS) or both. Method Regional alpha(1)-adrenoceptor vasoreactivity was measured using a graded brachial artery infusion of the alpha 1 agonist, phenylephrine, in seven subjects with stage 1 hypertension. Forearm blood flow was estimated from venous occlusion plethysmography. The phenylephrine dose-forearm blood flow response curve was used to determine alpha(1)-vascular reactivity ( slope of the dose response curve) and sensitivity, EC50 ( phenylephrine dose inducing 50% maximal response). BRS (ms/mmHg) was measured as the slope of the progressive rise in systolic blood pressure and the resultant lengthening in the subsequent R-R interval after systemic intravenous boluses of phenylephrine. Subsequently, plasma lipids were raised with a 1-h systemic co-infusion of intralipid and heparin, after which measurements of regional vasoreactivity and BRS were repeated. Results Mean arterial pressure was 109 W 4 versus 110 +/- 3 (P = NS), vasoreactivity was -0.71 +/- 0.10 versus -0.82 +/- 0.10 (P = NS) and log EC50 was 1.47 +/- 0.29 versus 1.52 +/- 0.34 nmol/l (P = NS) before and after raising non-esterified fatty acids, respectively. In contrast, mean BRS was acutely reduced from 8.2 +/- 2.1 to 6.2 +/- 1.8 ms/mmHg (P = 0.02) after the lipid infusion. Conclusions These findings suggest that in hypertensive patients, the primary mechanism for short-term alpha(1)-pressor hypersensitivity in response to hyperlipidemia is via the acute impairment of BRS. J Hypertens 24:1383-1389 (c) 2006 Lippincott Williams & Wilkins.