ENDOTHELIUM-MEDIATED AND DIRECT ACTIONS OF ACETYLCHOLINE ON RABBIT AORTIC BARORECEPTORS

Effects of exogenous acetylcholine on single-unit aortic baroreceptors were studied using a rabbit in vitro aortic arch/aortic nerve prepara tion. The arch was perfused with Krebs-Henseleit solution at constant pressure while simultaneously recording arch diameter and baroreceptor discharge frequency. Administration of acetylcholine over a wide rang e of concentrations (10(-9) to 10(-4) mol/L) evoked multiple dose-depe ndent changes in baroreceptor activity. ''Low'' concentrations (<10(-6 ) mol/L) consistently dilated arch and increased baroreceptor discharg e (n=11). These responses were prevented by prerelaxing smooth muscle with sodium nitroprusside (10(-7) mol/L, n=6) and were augmented by pr econtracting smooth muscle with norepinephrine (0.5 x 10(-7) mol/L, n= 11). Thus, the baroreceptor responses were dependent quantitatively on the level of preexisting vasoactive tone. The responses also were ant agonized by atropine (10(-7) mol/L, n=6), which inhibits release of en dothelium-derived relaxing factor (EDRF), and by N-monomethyl-L-argini ne (10(-5) mol/L, n=6), a specific blocker of nitric oxide formation ( primary relaxing factor responsible for acetylcholine vasorelaxation). Hexamethonium was ineffective (n=6). These results indicate that ''lo w-dose'' responses to acetylcholine were mediated solely by release of EDRF. In contrast, ''high'' concentrations of acetylcholine (>10(-6) mol/L) constricted arch and reduced baroreceptor discharge in most uni ts (66%). These responses were blocked by atropine, but not by hexamet honium, and were attributed to direct contraction of the smooth muscle . In the remaining baroreceptors (33%), discharge increased irrespecti ve of changes in diameter or preexisting vasoactive tone, but not in t he presence of hexamethonium. Therefore, some baroreceptors were stimu lated chemically by acetylcholine (or an intermediary substance), prob ably through activation of nicotinic receptors on the sensory endings. The effects of acetylcholine on the baroreceptor pressure-frequency c urve also were examined by injecting slow pressure ramps before and du ring acetylcholine treatment. Low concentrations that relaxed smooth m uscle shifted the curve to lower pressures; high concentrations that c ontracted smooth muscle shifted the curve to higher pressures. Last, w hen acetylcholine was given with the diameter rather than the pressure held constant, the baroreceptor reciprocal responses to smooth muscle relaxation and contraction were directionally reversed but remained c onsistent with the changes in wall tension. In summary, acetylcholine altered baroreceptor discharge through three mechanisms: (1) endotheli um-mediated vasorelaxation, which either increased or decreased discha rge depending on the directional change in wall tension, (2) direct sm ooth muscle contraction, which had the opposite effect as relaxation, but only at high concentrations, and (3) chemical activation, which oc curred in a minority of baroreceptors and also only at high concentrat ions. (Circ Res. 1994;74:422-433.)