Microvascular effects of atrial natriuretic factor: interaction with alpha 1- and alpha 2-adrenoceptors.

Abstract

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 micron), large capacitance venules (147 +/- 8 micron), and small terminal arterioles (17 +/- 1 micron). 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 X 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 alpha 1-adrenoceptor agonist, phenylephrine, in the presence of 5 X 10(-7) M yohimbine. However, vessels constricted with the alpha 2-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 alpha-receptor agonists. Significant dilation occurred at greater than 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 alpha 1-adrenoceptor-mediated constriction of large arterioles and venules. Constriction produced by alpha 2-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 alpha 1-, alpha 2-, 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.

Effect of Atrial Natriuretic Factor on Skin Microcirculation Versus Skeletal Muscle Blood Flow

“…In vivo studies with selective a r and a 2-agonists have sup ported the concept of heterogeneity of postjunc tional a-adrenoceptors in human vasculature. Faber and colleagues demonstrated that A N F was highly potent in selectively reversing a r adrenoceptormediated constriction (13), but in their study a 2-adrenoceptor-m ediated constriction was ANF in sensitive, which may explain the absence of an ef fect of A N F on cold-induced vasoconstriction in our study. Our experiments with postocclusive re active hyperem ia indicate that A N F apparently does not modulate microvascular vasodilator func tion.…”

Effect of Atrial Natriuretic Peptide on Hemodynamics of the Stage 21 Chick Embryo

“…Rather, they found that ANP increased the vascular resistance to venous return, indicative of vascular constriction instead of dilation. Recently, Faber et al (22), using denervated skeletal muscle in microscopic observation, reported that ANP increased diameters of the large distributing arterioles and capacitance venules preconstricted by a-1 agonist, and also dilated the intact small terminal arterioles. In general, vascular constriction causes an increase of blood pressure, even if only transiently; this was not seen in our study.…”

Effect of endopeptidase‐24.11 inhibitors and C‐ANP receptor ligand on responses evoked in arterioles of rat cremaster muscle by atrial natriuretic peptide

“…Sarelius & Huxley (1990) have shown that ANP can produce vasodilatation of terminal arterioles in the hamster cheek pouch. However, other investigators have found in the rat that terminal arterioles do not respond (Proctor & Bealer, 1987) or only minimally to topically applied ANP (Faber et al, 1988). Accordingly, in this study, we examined the effect of ANP on the diameter of skeletal vessels.…”