Enhanced pulmonary alpha-2 adrenoceptor responsiveness under conditions of elevated pulmonary vascular tone.
Alpha-1 and alpha-2 adrenoceptor-mediated vasoconstriction was studied in the in situ, autoperfused pulmonary circulation of the open-chest anesthetized dog under conditions of normal and elevated pulmonary vascular tone. Under conditions of normal pulmonary vascular tone (10 +/- 1 mm Hg), methoxamine, a selective alpha-1 adrenoceptor agonist, and B-HT 933, a selective alpha-2 adrenoceptor agonist, elicited maximal increases in lobar perfusion pressure of 5 and 2 mm Hg above resting pulmonary tone, respectively. When pulmonary vascular tone was elevated progressively with the thromboxane mimetic, U-46619, serotonin or PGF2 alpha, alpha-1 adrenoceptor-mediated pulmonary vasoconstrictor responses to methoxamine were unaffected, whereas alpha-2 adrenoceptor-mediated pulmonary pressor responses to B-HT 933 were enhanced. Overall the response to B-HT 933 was enhanced 4-fold when pulmonary perfusion pressure was elevated to 19.8 +/- 0.8 mm Hg with U-46619 and almost 5-fold when elevated to 27.0 +/- 1.2 mm Hg. Pulmonary vasoconstrictor responses to angiotensin II were unaffected by elevated pulmonary vascular tone. Enhanced responsiveness of B-HT 933 to elevated pulmonary vascular tone was antagonized by the selective alpha-2 adrenoceptor antagonist, rauwolscine (100 micrograms/kg i.v.), and unaffected by the selective alpha-1 adrenoceptor antagonist, prazosin (100 micrograms/kg i.v.). When canine intralobar pulmonary veins were studied in vitro they contracted to B-HT 933 whereas intralobar pulmonary arteries did not respond. These data indicate that alpha-2 adrenoceptor responsiveness is enhanced markedly and selectively under conditions in which pulmonary vascular tone is elevated.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D015237:Dinoprost; D004285:Dogs; D005260:Female; D008168:Lung / Q000098:blood supply*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D001381:Azepines; D011450:Prostaglandin Endoperoxides, Synthetic; D011460:Prostaglandins F; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D012701:Serotonin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost; C015603:azepexole; D008729:Methoxamine; D011224:Prazosin