Mechanism of vasodilation induced by alpha‐human atrial natriuretic polypeptide in rabbit and guinea‐pig renal arteries.

Abstract

SUMMARY1. Effects of a-human atrial natriuretic polypeptide (a-HANP) on electrical and mechanical properties of smooth muscle cells of the guinea-pig and rabbit renal arteries and of the guinea-pig mesenteric artery were investigated.2. a-HANP (up to 10 nM) modified neither the membrane potential nor resistance of smooth muscle cells of the guinea-pig and rabbit renal arteries. In the guinea-pig mesenteric and renal arteries, a-HANP (up to 10 nm) had no effect on the amplitude and facilitation (mesenteric artery) or depression (renal artery) ofexcitatory junction potentials nor on action potentials.3. In the guinea-pig renal artery, a-HANP (up to 10 ni) had no effect on the depolarizations induced by noradrenaline (NA) (up to 10 FM) but markedly inhibited NA-induced contraction. a-HANP (10 nM) slightly inhibited the K-induced contraction. In the rabbit renal artery, a-HANP (10 nM) inhibited the NA-induced contraction and to a lesser extent the K-induced contraction. 4. In the rabbit renal artery, the effects of a-HANP on the release of Ca from the cellular storage by two applications of NA, and its re-storage, were investigated in Ca-free solution containing 2 mM-EGTA. When 5 nm-a-HANP was applied before and during the first application of0-5 ,uM-NA, the contraction was markedly inhibited but the contraction to a second application of 10,uM-NA was potentiated. If the first dose of NA was 10 /M the effect was very small. Under the same experimental procedures, nitroglycerine (10 /M) showed almost the same effects as o-HANP on the NA-induced contractions. When both the first (3 mM) and second (10 mM) contractions were evoked by caffeine in Ca-free solution, a-HANP (5 nM) and nitroglycerine (10 ,M) inhibited both contractions to the same extent.5. In the rabbit renal artery, applications of a-HANP or nitroglycerine increased the amount of guanosine 3',5'-phosphate (cyclic GMP) in a dose-dependent manner. However, a much higher concentration of nitroglycerine was required (2 x 103 times).6. In the rabbit renal artery, hydrolysis of phosphatidyl inositol 4,5-bisphosphate (PI-P2) activated by 0 5 1sM-NA was inhibited by a-HANP, in a dose-dependent manner, but activation by 10 /sM-NA was not inhibited by a-HANP (up to 100 nm).

Bronchodilator and pre‐protective effects of urodilatin in bovine bronchi in vitro: comparison with atrial natriuretic peptide

“…The time course of the peak increases in cyclic GMP coincides with the peak relaxant effect (attained in around 5 min), an observation in agreement with that of Ishii & Murad (1989). The mechanism by which cyclic GMP may induce relaxation remains to be elucidated, however, some reports suggest modulation of transmembrane mobilisation of Ca2", possibly through activation of a calcium extrusion pump (Popescu et al, 1985;Ishihera et al, 1985;Fujii et al, 1986). In summary, this investigation suggests, for the first time, a role for both the elevation of cyclic GMP and the opening of ATP-sensitive and small conductance calcium-activated K+ channels in response to urodilatin.…”

Possible involvement of sodium pump in the relaxation of rat aorta induced by .ALPHA.-human atrial natriuretic polypeptide.

“…For example, besides the action observed here, it is reported that the peptides inhibited the release of calcium from intracellular stores of vascular smooth muscles (Fujii et al, 1986;MEISHERI et al, 1986) or stimulated calcium extrusion from the cells (Fujii et al, 1986). The concentration of a-hANP used in the present study was comparable to or lower than that required to produce the above actions.…”

“…SATO et al mediate the action in each tissue WINQuIsT et a!., 1984), the cellular or molecular mechanisms of actions of the peptides have not been fully elucidated. As for its vasorelaxing action, some mechanisms are postulated, such as an inhibition of Ca release from intracellular stores (CHID et al, 1986;FuJII et al, 1986;MEISHERI et al, 1986), acceleration of Ca extrusion from cells (FuJII et al, 1986;WINQUIST, 1986), or a blockade of receptor-operated Ca channels (CHID et al, 1986;WINQUIST, 1986). Unlike endogenous digitalis-like substance (HARDY et al, 1979;HAMLYN et al, 1982) which also causes natriuresis possibly through inhibition of the Na, KATPase in a nephron, atrial peptides do not inhibit the enzyme (THIBAULT et al, 1983;PAMNANI et a!.,1984;AALKJAER et a!., 1985).…”

Interaction between Flow-Induced Prostacyclin Production and Nitric Oxide Synthesis in Vascular Smooth Muscle Cells.

“…Second, flow-induced NO production was less in SHR than in WKY. Moreover, recent evidence (28)(29)(30)(31)(32)(33) has shown that 8-bromo-cyclic GMP, sodium nitroprusside, and atrial natriuretic peptide attenuate phosphatidylinositol turnover in platelets and vascular tissues, and that cyclic GMP inhibits the interactions between GTP-binding protein and PLC in cultured aortic VSMC. Because NO may suppress PLC activity and because PLC may be one main source of AA release during shear stress, less NO production may result in less inhibition of PLC activity, which would increase prostacyclin formation in SHR but not in WKY.…”