Alpha-1B adrenoceptors mediate neurogenic constriction in mesenteric arteries of normotensive and DOCA-salt hypertensive mice

Abstract

The contribution of alpha-1 adrenergic receptor (α 1-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 μM), PPADS (10 μM), yohimbine (1 μM), 5-methylurapidil (5-MU; 0.1 μM), L-765,314 (1 μM) and BMY-7378 (0.3 μM); selective antagonists at α 1-, P2X, α 2-, α 1A-, α 1B-, and α 1D-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 α 1B-and to a lesser extent at α 1A-ARs in SHAM arteries whereas NE mediates neurogenic constrictions in DOCA-salt arteries by acting at α 1B-ARs.