Sympathectomy inhibits the vasoactive effects of nicotine in conscious rats.
OBJECTIVE
The mechanisms underlying the pressor response to nicotine are incompletely understood. Although sympatho-adrenergic activation plays a major role, the relative contribution of adrenal vs. neurally released catecholamines and the possible role of non-adrenergic factors (e.g. vasopressin release) is not established.


METHODS
We examined the cardiovascular responses to graded i.v. injections of nicotine (1 to 100 micrograms kg-1) in conscious Wistar-Kyoto rats under control conditions and (i) after chemical sympathectomy by 6-hydroxydopamine, which destroys sympathetic endings but spares the adrenal medulla; (ii) after an alpha-adrenergic blockade by phenoxybenzamine; (iii) after a V1 vasopressin receptor blockade by a specific antagonist.


RESULTS
In control rats, nicotine caused a dose-dependent tachycardiac and pressor response. Both responses were abolished by sympathectomy, whereas the alpha-blockade left the tachycardiac response unaffected but inhibited the pressor response: the V1 vasopressin receptor blockade had no effect on either the tachycardiac or pressor response.


CONCLUSIONS
We conclude that in the conscious rat; (1) the pressor response to nicotine mainly depends on peripheral alpha-adrenergically-mediated vasoconstriction; (2) the vasomotor effect is caused by neural rather than adrenomedullary catecholamine release; (3) the nicotine-induced increase in heart rate (and presumably cardiac output) is per se unable to raise blood pressure, and (4) the nicotine-induced release of vasopressin plays no significant role in the pressor response.
Marano
G
G
Laboratorio di Farmacologia, Istituto Superiore di Sanitá, Roma, Italy. gmarano@net.iss.it
Ramirez
A
A
Mori
I
I
Ferrari
A U
AU
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D016627:Oxidopamine; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D013563:Sympathectomy, Chemical; D013565:Sympatholytics
D000317:Adrenergic alpha-Antagonists; D065092:Antidiuretic Hormone Receptor Antagonists; D005731:Ganglionic Stimulants; D013565:Sympatholytics; D010643:Phenoxybenzamine; D001127:Arginine Vasopressin; D009538:Nicotine; D016627:Oxidopamine