Vasoactive effects of substance P on isolated rabbit pulmonary artery.
The vasoactive properties of substance P (SP) were studied in isolated rabbit pulmonary artery (PA) segments in vitro. In the absence of active base-line tone, noncumulative administration of SP (10(-11) to 10(-4) M) produced dose-dependent increases in PA tension. The peak isometric tension (Tmax) with SP was similar to the Tmax response to epinephrine; however, the doses of the agonist producing a threshold contraction and 25% of Tmax (ED25) were significantly lower for SP. In the presence of active base-line tone, induced by epinephrine or 5-hydroxytryptamine, SP produced transient PA relaxation which was directly related to the magnitude of the precontracted PA tension. Blockade of neurotransmission with tetrodotoxin (1 microgram/ml) and antagonists to alpha 1-adrenergic and histamine receptor binding had no effect on the contractile response to SP. On the other hand, PA contraction to an ED50 dose of SP was 1) inhibited by a mean of 33 +/- 10% (SE) following pretreatment with the cholinesterase inhibitor, neostigmine (10(-6) M) and 2) augmented by 52 +/- 21% with the cholinergic antagonist, atropine (10(-4) M). The latter also completely blocked the relaxation response to SP in precontracted PA. Similarly, removal of the PA endothelium also abolished the relaxation response to SP. In contrast, SP-induced contraction was markedly inhibited by the cyclooxygenase inhibitor, meclofenamate (1 microgram/ml), as well as the SP antagonist, D-Pro2, D-Trp7,9-SP.(ABSTRACT TRUNCATED AT 250 WORDS)
Tanaka
D T
DT
Grunstein
M M
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D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001696:Biomechanical Phenomena; D002744:Chlorpheniramine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008469:Meclofenamic Acid / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009388:Neostigmine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects*; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
D012701:Serotonin; D013373:Substance P; D009388:Neostigmine; D002744:Chlorpheniramine; D013779:Tetrodotoxin; D008469:Meclofenamic Acid; D001285:Atropine; D002927:Cimetidine; D004837:Epinephrine; D010646:Phentolamine