Microvascular Effects of Atrial Natriuretic Factor: Interaction With α1- and α2-Adrenoceptors

• Published in: Circulation research 1988-08, Vol.63 (2), p.415-428
• Main Authors: Faber, James E, Gettes, David R, Gianturco, Daniel P
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Vertebrates: cardiovascular system
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.63.2.415

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 microcirculationlarge distributing arterioles (x control diameter = 100 ± 7 μm), large capacitance venules (147 ± 8 μm), and small terminal arterioles (17 ±1 μm). 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 IC25 = 18 pmol and IC50=1.2 ± 10-10 M; venules exhibited similar sensitivity. However, the highest ANF concentration examined (10-7 M) only reversed NE-induced tone by 70%. In a second large vessel group ANF completely reversed constriction induced by the α1-adrenoceptor agonist, phenylephrine, in the presence of 5 ± 10-7 M yohimbine. However, vessels constricted with the α2-receptor agonist UK-14,304 (in the presence of 10-8 M prazosin) were insensitive to ANF. A third group of terminal arterioles, which possess considerable spontaneous "intrinsic" tone, were studied in the absence of α-receptor agonists. Significant dilation occurred at >10-7 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 α1-adrenoceptor-mediated constriction of large arterioles and venules. Constriction produced by α2-adrenoceptor 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 α1-, α2-, 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.