In vitro Analysis of Alpha-Adrenoceptor Interactions with the Myogenic Response in Resistance Vessels

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Abstract
The interaction of α1- and α2-adrenoceptor constriction of isolated rat cremaster small arteries (mean diameter ± SEM, 114 ± 5 µm) with the myogenic mechanism was examined with in vitro videomicroscopy. Microdissected vessels were double-cannulated with glass micropipets in a tissue bath, and intra-luminal pressure was set at 65 mm Hg baseline pressure. Norepinephrine (NE) concentration-response curves were obtained alone and in the presence of prazosin or rauwolscine to establish the concentrations of NE required to selectively stimulate α1- or α2-adrenoceptors. A bimodal response was produced by NE alone, indicating interaction with more than one receptor population. Rauwolscine and prazosin each produced dextral displacement at low &(M)NE concentrations. However, while prazosin exhibited competitive antagonism, rauwolscine did not antagonize NE at concentrations ≧ EC50 value. Thus, both α1 and α2-adrenoceptors mediate constriction at low NE concentrations, but only α1-receptors contributed to constriction at intermediate and high concentrations. These data are in contrast to previous findings for the same vessels studied in vivo. Diameter responses to increases and decreases in transmural pressure from baseline were examined in the relaxed (passive) state with nitroprusside present, during spontaneous intrinsic tone, and during induced α1- or α2-tone (EC20 concentration of NE plus rauwolscine or prazosin). Myogenic constriction during increases in lumen pressure and myogenic inhibition of tone during decreases in pressure were greatest during α1-tone, less during intrinsic tone and least during α1-tone. These findings suggest that local pressure-dependent autoregulatory mechanisms may be modulated by the type of α-adrenoceptors and relative activation that predominate within the different vascular segments of a particular tissue.

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