Differential activation of α1- and α2-adrenoceptors on microvascular smooth muscle during sympathetic nerve stimulation

Abstract

The relative contribution of postjunctional α1- and α2-adrenoceptors to constriction of microvessels was examined during sympathetic nerve stimulation and sympathetic escape (difference between peak and steady-state constriction). Large arterioles (120 ± 4 μm control diameter) and venules (174 ± 6 μm) and small arterioles (13 ± 4 μm) were examined in rat cremaster skeletal muscle during stimulation of the cremaster efferent innervation (decentralized lumbar sympathetic chain, 0.5-16 Hz, 2-minute train). The muscle was suspended in a tissue bath, and diameter was measured with intravital microscopy. Frequency-response curves were obtained after vehicle (prazosin or rauwolscine) was added to the bath. In large arterioles, prazosin (10-7 M) significantly attenuated constriction by 60-80%; a fivefold higher concentration had no additional effect. In contrast, rauwolscine (1 to 5 x 10-7 M) had no effect. Venules evidenced minimal response to nerve stimulation. In small arterioles, rauwolscine (5 x 10-7 M) significantly attenuated constriction by 50-60%, while prazosin (10-7 M) had no effect. These data suggest that for large arterioles, which are known to possess both receptors, α1-adrenoceptors are preferentially stimulated by nerve-released norepinephrine. In contrast, sympathetic constriction of small arterioles is mediated by α2-adrenoceptors. Compared with large arterioles, small arterioles exhibited greater peak and steady-state constriction at all frequencies, with maximal responses achieved over the 0.5-4 Hz range. Large arterioles exhibit graded constriction over the entire frequency range. Sympathetic escape exhibited a small, negatively correlated frequency dependence for large arterioles, tended to be greater for small arterioles, and was more evident in large arterioles during α2-adrenoceptor constriction at low-frequency stimulation. This distinct neural control of large resistance vessels by α1-adrenoceptors and small terminal arterioles by α2-adrenoceptors may allow neurogenic regulation of these vessel segments to be differentially susceptible to modulation by other extrinsic and intrinsic vasoactive controls that preferentially interact with α1- and α2-adrenergic contractile mechanisms.