Mj. Goldberg et al., LOCAL AND SYSTEMIC PHENTOLAMINE ANTAGONISM OF NOREPINEPHRINE-INDUCED HAND VEIN CONSTRICTION, Journal of clinical pharmacology, 35(2), 1995, pp. 170-175
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.