Alpha-1B adrenoceptors mediate neurogenic constriction in mesenteric arteries of normotensive and DOCA-salt hypertensive mice.
The contribution of alpha-1 adrenergic receptor (alpha1-AR) subtypes to neurogenic constrictions of mesenteric resistance arteries from SHAM and deoxycorticosterone acetate-salt (DOCA-salt) hypertensive mice was assessed. Frequency-response curves (0.5-30 Hz) for transmural stimulation-evoked contractions were examined in SHAM and DOCA-salt arteries in vitro in the absence (control) and presence of prazosin (0.1 microM), PPADS (10 microM), yohimbine (1 microM), 5-methylurapidil (5-MU; 0.1 microM), L-765,314 (1 microM) and BMY-7378 (0.3 microM); selective antagonists at alpha1-, P2X, alpha2-, alpha1A-, alpha1B-, and alpha1D-AR, respectively. In SHAM arteries, prazosin but not PPADS inhibited neurogenic responses. L-765,314 substantially inhibited neurogenic responses while 5-MU had a small inhibitory effect. BMY-7378 did not alter contractile responses at all. In DOCA-salt arteries, prazosin reduced neurogenic responses with no further significant inhibition seen with PPADS. L-765,314 antagonized neurogenic constrictions to a level similar to that seen in SHAM arteries. Furthermore, 5-MU and BMY-7378 did not affect these responses. The density of noradrenergic nerves (assessed using glyoxylic acid-induced fluorescence) or norepinephrine (NE) content was not altered by DOCA-salt hypertension. These results indicate that NE is the primary mediator of neurogenic constriction of murine mesenteric arteries. Nerve-released NE acts primarily at alpha1B-and to a lesser extent at alpha1A-ARs in SHAM arteries whereas NE mediates neurogenic constrictions in DOCA-salt arteries by acting at alpha1B-ARs.
Pérez-Rivera
Alex A
AA
Department of Pharmacology and Toxicology, Michigan State University, B 328 Life Sciences Building, East Lansing, MI 48824, USA. perezriv@msu.edu
Fink
Gregory D
GD
Galligan
James J
JJ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003900:Desoxycorticosterone; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D006973:Hypertension / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
C547717:Adra1b protein, mouse; D000317:Adrenergic alpha-Antagonists; D010975:Platelet Aggregation Inhibitors; D018340:Receptors, Adrenergic, alpha-1; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D015016:Yohimbine; D003900:Desoxycorticosterone; D011732:Pyridoxal Phosphate; D009638:Norepinephrine