Mechanism of lipid enhancement of alpha1-adrenoceptor pressor sensitivity in hypertension.
OBJECTIVE
Plasma lipids enhance alpha1-adrenoceptor pressor sensitivity, impair baroreflex function, and correlate with increased blood pressure. This clinical study was designed to determine whether the enhanced alpha1-pressor sensitivity induced by acute hyperlipidemia is primarily mediated by increased vascular alpha1 responsiveness, reduced baroreflex sensitivity (BRS) or both.


METHODS
Regional alpha1-adrenoceptor vasoreactivity was measured using a graded brachial artery infusion of the alpha1 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 alpha1-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 +/- 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 alpha1-pressor hypersensitivity in response to hyperlipidemia is via the acute impairment of BRS.
Gadegbeku
Crystal A
CA
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109-0725, USA. cgadegbe@umich.edu
Shrayyef
M Zakarea
MZ
Taylor
Timothy P
TP
Egan
Brent M
BM
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced / Q000503:physiopathology*; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010656:Phenylephrine / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D014280:Triglycerides / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D005230:Fatty Acids, Nonesterified; D018340:Receptors, Adrenergic, alpha-1; D014280:Triglycerides; D010656:Phenylephrine