Direct and sympathetically mediated venoconstriction in essential hypertension. Enhanced responses to endothelin-1.
Endothelin-1 is a potent endothelium-derived vasoconstrictor peptide. Although circulating concentrations are not increased in essential hypertension, enhanced sensitivity to endothelin-1 has been observed in animal models of hypertension. We investigated dorsal hand vein responses to local infusion of endothelin-1 and norepinephrine in 12 patients with essential hypertension who had never received treatment and in 12 age and sex matched normotensive control subjects. The maximal venoconstriction and the geometric mean of the dose of norepinephrine that caused 50% of maximal venoconstriction were similar in hypertensive (mean +/- SE; 80 +/- 4%; 31 +/- 8 pmol/min) and normotensive subjects (87 +/- 5%, 22 +/- 9 pmol/min). In contrast, mean venoconstriction to endothelin-1 was significantly greater in hypertensive (49 +/- 5%) than in normotensive subjects (27 +/- 2%; P = 0.004). Sympathetically mediated venoconstriction elicited by deep breath was substantially potentiated by endothelin-1 in hypertensive (67 +/- 7% at 90 min) but not normotensive subjects (11 +/- 3% at 90 min; P = 0.001). Venoconstriction to endothelin-1 correlated positively with mean arterial pressure in the hypertensive subjects (r = 0.82; p = 0.001) but negatively in the normotensive subjects (r = -0.58; p = 0.047). Endothelin-1 may contribute to the reduction of venous compliance occurring in the early stages of essential hypertension and to the altered systemic hemodynamics in this condition.
Haynes
W G
WG
Department of Medicine, University of Edinburgh, Western General Hospital, United Kingdom.
Hand
M F
MF
Johnstone
H A
HA
Padfield
P L
PL
Webb
D J
DJ
D000328:Adult; D001794:Blood Pressure; D016232:Endothelins / Q000097:blood / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D006225:Hand / Q000098:blood supply; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology; D012119:Respiration; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects*; D014680:Veins
D016232:Endothelins; D009638:Norepinephrine