LOCAL AND SYSTEMIC PHENTOLAMINE ANTAGONISM OF NOREPINEPHRINE-INDUCED HAND VEIN CONSTRICTION

The dorsal hand Vein distention technique has been used to study the e ffects of alpha-adrenergic receptor antagonists on alpha-agonist-induc ed venoconstriction. Using this technique, we investigated the dose-ef fect relationships between different intravenous routes of phentolamin e (an alpha-antagonist) administration on norepinephrine (an alpha-ago nist)-induced hand vein constriction. Hand vein studies were done on h ealthy men; each man was studied on up to four occasions. On one occas ion for each man, graded doses of phentolamine were infused into a han d vein preconstricted (submaximally) with norepinephrine. The dose of phentolamine producing a half maximal response (ED(50)) for reversal o f venoconstriction, and the maximal reversal were calculated. On the o ther three occasions (randomly allocated) for each man, graded doses o f norepinephrine were infused into a hand vein before and during intra venous infusions of (1) control (vehicle solutions); (2) systemic (oth er arm vein) phentolamine; and (3) local (hand vein) phentolamine. Sys temic and local phentolamine dose ratios (ED(50) of norepinephrine dur ing phentolamine, divided by ED(50) of norepinephrine before phentolam ine; divided by the control dose ratio) were calculated. These studies show that phentolamine (administered directly into a preconstricted h and vein) can completely reverse norepinephrine-induced venoconstricti on. Phentolamine, administered by either local or systemic intravenous infusion, induces a significant rightward shift (approximately 10-fol d) in responsiveness to norepinephrine-induced venoconstriction. To ac hieve comparable degrees of alpha-antagonism, however, systemic phento lamine must be administered intravenously at a dose approximately 3,00 0-fold higher than that of local phentolamine. Implications of these d ose-effect relationships, and their possible application to the treatm ent of norepinephrine extravasation and to hand vein studies with othe r receptor agonist-antagonist combinations, are discussed.