Mechanisms underlying constrictor and dilator responses to perivascular nerve stimulation in canine lingual arteries.
In isolated canine lingual arteries denuded of the endothelium, transmural electrical stimulation (2-20 Hz) produced a frequency-related contraction which was not significantly influenced by prazosin but which was reversed to a relaxation by alpha,beta-methylene ATP. The responses were abolished by tetrodotoxin. The stimulation-induced relaxation was abolished by treatment with NG-nitro-L-arginine (L-NA, 10(-6) M) and restored by the addition of L-arginine. Neurogenic relaxation resistant to L-NA was not observed after electrical stimulation, even though the pulse width and stimulus intensity were raised. Under treatment with prazosin, alpha,beta-methylene ATP and indomethacin, the arterial strips responded to nicotine (10(-4) M) with a marked relaxation that was abolished by hexamethonium. The relaxation was significantly inhibited but not abolished by L-NA (10(-5) M), and raising the concentration of the inhibitor to 10(-4) M, did not produce additional inhibition. In the strips treated with L-NA, the nicotine-induced relaxation was abolished or markedly reduced under desensitization with vasoactive intestinal peptide (VIP) or calcitonin gene-related peptide (CGRP) and by treatment with high concentrations of beraprost, a stable analog of prostaglandin I2, but was unaffected by CGRP or VIP receptor antagonists. Relaxant responses to a low concentration of nicotine (5 x 10(-6) M) were abolished by L-NA and restored by L-arginine. Histochemical study demonstrated many nerve fibers and bundles containing NADPH diaphorase in the adventitia of the arteries. It is concluded that the neurogenic arterial contraction is induced mainly by ATP via stimulation of P2X purinoceptors, and that the relaxation induced by electrical stimulation or a low concentration of nicotine is mediated by nitric oxide (NO) released from perivascular nerves. In high concentrations, nicotine elicits marked relaxations possibly due to the liberation of NO from the nerve and also vasodilator substances that increase the content of cyclic AMP in the tissue. CGRP and VIP are unlikely to be involved.
Okamura
T
T
Department of Pharmacology, Shiga University of Medical Science, Seta, Ohtsu, Japan.
Ayajiki
K
K
Uchiyama
M
M
Kagami
K
K
Toda
N
N
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000294:innervation; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D005731:Ganglionic Stimulants / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D014059:Tongue / Q000098:blood supply* / Q000294:innervation; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D005731:Ganglionic Stimulants; D009538:Nicotine; D000255:Adenosine Triphosphate; D015237:Dinoprost; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D011224:Prazosin