Microvascular Effects of Atrial Natriuretic Factor : Interaction With ax - and a 2 - Adrenoceptors

The cremaster skeletal muscle of anesthetized rats was denervated and extended with intact circulation into a tissue bath. Intravital microscopy was used to measure microvessel diameter at three different anatomical levels within the microcirculation: large distributing arterioles (x control diameter = 100 ± 7 /nn), large capacitance venules (147 ± 8 /tin), and small terminal arterioles (17 ± 1 fim). Norepinephrine (NE) was added to the cremaster bath to produce intermediate reductions in diameter of large arterioles and venules (55% and 38% of maximum constriction, respectively). In the presence of NE tone, bath-added atrial natriuretic factor (ANF) produced concentration-dependent dilation of both arterioles and venules. Arteriolar 1(̂ 25 = 18 pmol and ICso = 1.2x 10~ M; venules exhibited similar sensitivity. However, the highest ANF concentration examined (10~ M) only reversed NE-induced tone by 70%. In a second large vessel group ANF completely reversed constriction induced by the a,-adrenoceptor agonist, phenylephrine, hi the presence of 5 x 10" M yohimbine. However, vessels constricted with the aj-receptor agonist UK-14,304 (in the presence of 10" M prazosin) were insensitive to ANF. A third group of terminal arterioles, which possess considerable spontaneous "intrinsic" tone, were studied in the absence of a-receptor agonists. Significant dilation occurred at >10~ M, and the maximal response was only 25% of complete dilation with adenosine. These data indicate that ANF exhibits a high potency and selectivity for reversal of a,-adrenoceptormediated constriction of large arterioles and venules. Constriction produced by a2adrenoceptor occupation or by nonadrenergic "intrinsic" mechanisms appears to be insensitive to ANF. We propose that the ability of ANF to reduce microvascular resistance depends on the relative contribution of a,-, a2-, and intrinsic vasoconstrictor components to the prevailing level of smooth muscle tone. Differences in these components among regional circulations and between arterial and venous smooth muscle may contribute to the systemic hemodynamic pattern produced by ANF. (Circulation Research 1988;63:415-428)