Pharmacological characterization of alpha 1-adrenoceptor subtype mediating regulation of arterial pressure and urethral perfusion pressure in the anaesthetized rat.
1. The alpha 1-adrenoceptor subtypes mediating the regulation of arterial pressure (AP) and urethral perfusion pressure (UP) in the anaesthetized rat were characterized by using selective alpha 1-adrenoceptor agonists and antagonists. 2. Intravenous administration of selective alpha 1-adrenoceptor agonists elicited a dose-dependent increase in AP and UP. The rank order of agonist potency: oxymetazoline (ED50, 6.2 and 8.2 nmol kg-1 > phenylephrine (ED50, 32 and 27 nmol kg-1 > methoxamine (ED50, 300 and 296 nmol kg-1 was the same for AP and UP, respectively. 3. The effects of phenylephrine on AP and UP were antagonized, in a dose related-manner, by pretreatment with alfuzosin, BMY 7378, 5-methyl-urapidil, phentolamine, prazosin, spiperone and WB 4101.5-methyl-urapidil was the only alpha 1-adrenoceptor antagonist more potent on UP than on AP. 4. The potency of the different alpha 1-adrenoceptor antagonists tested on AP and UP was significantly correlated with their binding affinity for the expressed recombinant alpha 1a-, but not alpha 1b- or alpha 1d-, adrenoceptor subtype. 5. The results suggest that in the anaesthetized rat (1) both AP and UP are regulated by the alpha 1A-adrenoceptor subtype; and (2) the urogenital selectivity of 5-methyl-urapidil may be due to the existence of multiple forms of the alpha 1A-adrenoceptor.
Guilmard
C
C
Institut Henri Beaufour Research Laboratorie, Les Ulis, France.
Auguet
M
M
Chabrier
P E
PE
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016014:Linear Models; D008297:Male; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011224:Prazosin / Q000037:antagonists & inhibitors / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000502:physiology; D014521:Urethra / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; C047638:alfuzosin; D011224:Prazosin