Sensory nerves, vascular endothelium and neurogenic relaxation of the guinea-pig isolated pulmonary artery.
1. In the presence of atropine and guanethidine (3 mumol/l each), electrical field stimulation (1-20 Hz) produced frequency-dependent relaxations of the histamine- (3 mumol/l) induced vascular tone in isolated rings from the guinea-pig pulmonary artery. The electrically-evoked relaxations were abolished by tetrodotoxin (1 mumol/l). The amplitude of these nerve-mediated, non-adrenergic non-cholinergic (NANC) relaxations was unaffected by removal of the vascular endothelium produced through rubbing of the internal surface. 2. Capsaicin (1 mumol/l) produced a prompt and sustained relaxation of the histamine-induced tone which was unaffected by removal of the endothelium. A second application of capsaicin 60-120 min later had no further relaxant effect, indicating desensitization. After in vitro capsaicin desensitization, the electrically-evoked NANC relaxations were abolished, both in the presence or absence of the vascular endothelium. 3. Substance P evoked a prompt and transient relaxation in precontracted arterial rings with intact endothelium and a transient small contraction in rings in which the endothelium had been mechanically removed. The selective NK-1 receptor agonist, [Pro9]-substance P sulfone closely mimicked the relaxation produced by substance P while the selective NK-2 or NK-3 receptor agonists had no relaxant effect. Tachyphylaxis to substance P did not modify the amplitude of the capsaicin-induced relaxation. 4. Human alpha calcitonin gene-related peptide (CGRP) produced a prompt and sustained relaxation both in the presence and absence of the vascular endothelium. 5. Ruthenium red (10 mumol/l) blocked the relaxation to capsaicin while leaving unaffected the relaxation to electrical field stimulation or CGRP (0.1 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
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CA
Maggi
R
R
Patacchini
F
F
Perretti
M
M
Tramontana
S
S
Manzini
P
P
Geppetti
P
P
Santicioli
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects*; D011651:Pulmonary Artery / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000378:metabolism / Q000502:physiology; D018039:Receptors, Tachykinin; D012430:Ruthenium Red / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology
D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D012430:Ruthenium Red; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin