Intra-arterial vasopressin in the human forearm: pharmacodynamics and the role of nitric oxide

Jonathan T Affolter, Sinéad P McKee, Ahmed Helmy, C Richard Jones, David E Newby, David J Webb

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND AND OBJECTIVES: Diverse vascular effects have been ascribed to vasopressin, including the potential to cause vasodilation, vasoconstriction, and nitric oxide release. The objective of this study was to establish the pharmacodynamics, reproducibility, and nitric oxide dependence of the vasomotor actions of vasopressin in the forearm resistance vessels.

METHODS: Blood flow in both forearms of 12 healthy men was measured with venous occlusion plethysmography. Continuous and discontinuous doses of 1 to 300 pmol/min vasopressin were administered by the intrabrachial route. For assessment of the contribution of nitric oxide, vasopressin was coadministered with a "nitric oxide clamp," a balanced coinfusion of 4 micromol/min L-N(G)-monomethylarginine (a nitric oxide synthase inhibitor) and 0.3 to 0.8 nmol/min sodium nitroprusside (an exogenous nitric oxide donor) to block endogenous nitric oxide production and restore normal basal blood flow, respectively.

RESULTS: Vasopressin produced a dose-dependent biphasic change in blood flow with a maximum reduction in percentage change in blood flow ratio of infused and control arms of 22% +/- 5% at 3 pmol/min (P <.01) and an increase of 80% +/- 30% at 300 pmol/min (P <.01). There were no significant differences in repeated responses obtained either within or between days. Repeated discontinuous dosing did not change the magnitude of the maximum vasoconstriction or vasodilation, but prolonged continuous infusion produced maximal vasodilation at 12 minutes that subsequently resulted in substantial tachyphylaxis (P =.04). Although there was no augmentation of vasoconstriction, the nitric oxide clamp abolished vasopressin-induced vasodilation (P <.05).

CONCLUSIONS: Intra-arterial vasopressin causes a reproducible dose-dependent biphasic change in forearm blood flow. Vasomotor responses are time-dependent with a modest delay to peak vasodilation and tachyphylaxis with prolonged sustained infusion. Nitric oxide release is a major contributor to vasopressin-induced vasodilation but does not directly oppose low-dose vasopressin-induced vasoconstriction.

Original languageEnglish
Pages (from-to)9-16
Number of pages8
JournalClinical pharmacology and therapeutics
Volume74
Issue number1
DOIs
Publication statusPublished - Jul 2003

Keywords

  • Adult
  • Analysis of Variance
  • Confidence Intervals
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Forearm
  • Humans
  • Injections, Intra-Arterial
  • Male
  • Middle Aged
  • Nitric Oxide
  • Vasomotor System
  • Vasopressins

Fingerprint Dive into the research topics of 'Intra-arterial vasopressin in the human forearm: pharmacodynamics and the role of nitric oxide'. Together they form a unique fingerprint.

Cite this