Human neuropeptide Y potentiates alpha1-adrenergic blood pressure responses in vivo.
Human neuropeptide Y (hNPY) potentiates the postjunctional vasoconstrictor effects of alpha1-adrenoceptor agonists in animals and in human hand veins in vivo. We therefore hypothesized that such an interaction might also occur in the human arterial bed. With the present single-blind cross-over study in 12 healthy volunteers, the effect of subpressor doses of hNPY on the blood pressure response to alpha1-adrenoceptor stimulation was evaluated. Dose-response curves were constructed to intravenously infuse phenylephrine with and without coinfusion with two different doses of hNPY (1.4 and 14.3 pmol . kg-1 . min-1). Blood pressure, heart rate, and forearm blood flow were recorded, and plasma hNPY was determined. During infusion of the higher hNPY dose, which increased hNPY from 24.0 +/- 12.0 to 495.1 +/- 12.6 pmol/l, blood pressure curves were 2.4-fold shifted toward lower phenylephrine dose rates (P < 0.001). Forearm vascular resistance showed a similar trend, whereas the counterregulatory decrease of heart rate was similar in both groups. In contrast, the lower hNPY dose rate producing a fourfold increase in hNPY concentrations did not modify the response to phenylephrine. This in vivo study in humans demonstrates that hNPY induced potentiating effects on alpha1-adrenergic constriction also in the systemic arterial circulation and suggests that circulating hNPY may participate in the control of vascular tone.
Division of Clinical Pharmacology, University Hospital, CH-4031 Basel, Switzerland.
L V
LV
Schuerch
L M
LM
Linder
E
E
Grouzmann
W E
WE
Haefeli
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D005542:Forearm / Q000098:blood supply; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000494:pharmacology*; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D009478:Neuropeptide Y; D010656:Phenylephrine