The nature of muscarinic receptor subtypes mediating pulmonary vasoconstriction in the rabbit.
The interaction of muscarinic receptor subtype-selective antagonists with ACh was studied in the pulmonary vasculature of rabbits. In anesthetized rabbits, ACh (5-20 nmol/kg, i.v.) increased pulmonary vascular resistance (PVR) and decreased systemic arterial pressure (SAP). After 2.85 nmol/kg i.v. pirenzepine (PNZ), the ACh-induced increase in PVR was attenuated by 67% while the decrease in SAP was not altered. After 2.85 mumol/kg i.v. pirenzepine, the ACh-induced increase in PVR was totally blocked, while the SAP response was only partially inhibited (43%). Similar results were obtained with trihexyphenidyl. Atropine or secoverine (SEC) inhibited equally the PVR and SAP responses to ACh. In isolated rabbit lungs perfused in situ at 140 ml/min, ACh (1 microM) increased PVR by 210%, perfusate levels of TXB2 by 1000% and 6-keto-PGF1 alpha by 21% of baseline values. PNZ (50 nM) inhibited the effects of ACh on PVR, TXB2 and 6-keto-PGF1 alpha levels. SEC (50 nM) did not alter the effects of ACh on PVR, or the TXB2 to 6-keto-PGF1 alpha ratio. At 100 nM, both PNZ and SEC reduced all effects of ACh. These results suggest that the rabbit pulmonary vascular muscarinic receptors mediating vasoconstriction and thromboxane release are sensitive to pirenzepine and thus behave more like M1 receptors.
el-Kashef
H
H
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta.
Catravas
J D
JD
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000097:blood / Q000378:metabolism; D008168:Lung / Q000098:blood supply*; D008297:Male; D018727:Muscarinic Antagonists; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000145:classification / Q000502:physiology*; D013931:Thromboxanes / Q000097:blood / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D013931:Thromboxanes; D011464:Epoprostenol; D000109:Acetylcholine