Sympathetic nervous system-dependent vasoconstriction in humans. Evidence for mechanistic role of endogenous purine compounds.
Purine compounds modulate sympathetic neurotransmission; this modulation decreases nervous discharge by stimulating presynaptic inhibitory adenosine receptors, an effect antagonized by theophylline, and causes vasoconstriction through the stimulation of postsynaptic ATP receptors. In humans we evaluated the effect of local theophylline, which was infused into the brachial artery at the rate of 100 micrograms/100 cc/min, on the arteriolar sympathetic vasoconstriction induced by applying a lower-body negative pressure. Forearm blood flow changes were measured by strain-gauge venous plethysmography. Theophylline, which at this dosage blunted the vasodilator effect of adenosine (the physiological agonist for the P1 purinoceptor), significantly increased lower-body negative pressure-mediated vasoconstriction. To evaluate whether neurotransmitters different from norepinephrine participate in the vasoconstrictor effect of theophylline, we repeated the previous experiment in the presence of phenoxybenzamine, which was infused at a dose (60 micrograms/100 cc/min) that abolished the vasoconstrictor effect of norepinephrine. Also, after alpha-adrenoceptor blockade, theophylline continued to increase sympathetic vasoconstriction. Our data confirm that purinergic receptors and neurotransmitters also participate in endogenous sympathetic vasoconstriction in humans.
Taddei
S
S
I Clinica Medica, University of Pisa, Italy.
Pedrinelli
R
R
Salvetti
A
A
D000241:Adenosine / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D010208:Papaverine / Q000494:pharmacology; D058914:Purinergic Antagonists; D011687:Purines / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000502:physiology*; D013806:Theophylline / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D058914:Purinergic Antagonists; D011687:Purines; D013806:Theophylline; D010208:Papaverine; D000241:Adenosine