Verapamil and alpha-mediated vasoconstriction in human forearm: a comparison between norepinephrine and selective alpha 1- and alpha 2-adrenergic agonists.
To evaluate the hypothesis of alpha-antagonism as a contributing factor to the vascular action of calcium entry blockade (CEB) in man, we have compared the action of verapamil, a CEB, on nonselective (norepinephrine, NE) and selective alpha 1-(methoxamine, MET) and alpha 2-(B-HT 933, BHT) adrenergic agonists in human forearm vasculature. All drugs were infused into the brachial artery at systemically ineffective rates. Blood pressure and heart rate were continuously monitored; forearm blood flow was measured through strain gauge plethysmography. Sixteen mild, untreated hypertensive patients were studied. Cumulative forearm blood flow dose-response curves to three cumulative infusion rates (3 min each) of NE (0.015, 0.05, 0.15 micrograms/100 ml tissue/min), MET (0.06, 0.6, 6 micrograms/100 ml tissue), and BHT (3, 10, 30 micrograms/100 ml tissue/min) were obtained during saline and after verapamil (0.9 micrograms/100 ml tissue/min X 15 min) infusion. Verapamil did not modify to any significant extent NE-mediated vasoconstriction, but clearly blunted the vascular action of either MET or BHT. Because NE is the physiological neurotransmitter, the data cast doubts about the relevance of alpha-antagonism as a mechanism of action of calcium entry blockade through verapamil. Besides, the data caution against generalizing by using data obtained through several compounds, including CEBs, of alpha-adrenergic stimuli.
Pedrinelli
R
R
Hypertension Unit, University of Pisa, Italy.
Taddei
S
S
Graziadei
L
L
Pana-Race
G
G
Salvetti
A
A
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D001381:Azepines / Q000494:pharmacology; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D014662:Vasoconstrictor Agents; D014700:Verapamil; C015603:azepexole; D008729:Methoxamine; D009638:Norepinephrine