Atrial natriuretic factor and cyclic guanosine 3',5'-monophosphate in vascular smooth muscle.

Abstract

SUMMARY To elucidate the molecular mechanism of the vascular action of atrial natriuretic factor (ANF), we investigated the effects of synthetic ANF and sodium nitroprusside on the levels of intracellular cyclic nucleotides and prostacyclin (measured as its stable metabolite 6-keto-prostaglandin F,a) in cultured vascular smooth muscle cells from rat mesenteric artery and, in some experiments, from rat renal artery. Both ANF and sodium nitroprusside increased intracellular cyclic guanosine 3',5'-monophosphate (cGMP) levels in a dose-dependent manner but did not affect cyclic adenosine 3',5'-monophosphate levels or 6-keto-prostaglandin F, tt synthesis. The stimulatory effects of ANF and sodium nitroprusside on cGMP levels were additive. Neither the deprivation of extracellular Ca

Atrial natriuretic peptide and urinary prostaglandins in man.

“…The mechanisms involved in the PG stimulation that we observed remain unclear. ANP has been shown to be unable to modify the in vitro 6-keto-PGFi,, biosynthesis by either human vascular endothelial (Abe et al, 1977) or rat mesenteric vascular (Sato et al, 1986) cultured cells which seems to exclude a direct effect. On the other hand, none of the main factors known to stimulate the renal PG biosynthesis (Levensson et al, 1982) seems to be clearly involved.…”

Cyclic GMP accumulation by atriopeptins in cultured rat renal and vascular smooth muscle cells.

“…Isolation and culture of cells VSM cells of mesenteric artery and RPCT cells were isolated and cultured from 150-200 g Sprague-Dawley rats as previously described (Sato and Dunn 1986 ;Sato et al 1986b). VSM cells at pasgage levels 3-9 and primary RPCT cells on days 4 or 5 of culture were used for experiments.…”

“…Experiments were terminated by removal of media, followed immediately by addition of 0.3 ml (or 0.2 ml for RPCT cells) of 0.1 N HC1. Cells were exposed to the HCl solution for 1 hr, intracellular cyclic nucleotides were extracted into the HC1 fraction, and part of the cellular protein was precipitated and left on the bottom of the culture dishes (Sato and Dunn 1986;Sato et al 1986b). …”

“…Radioimmunoassay of cGMP and cAMP were done in duplicate after succinylation using HC1 fraction or urine samples (Sato et al 1986b). PGE2 and 6-keto-PGFIa were measured by radioimmunoassay of the extracellular media using antisera as previously described (Sato and Dunn 1986;Sato et al 1986b).…”

“…ANP increases cGMP levels in various tissues including vasculature, adrenal gland and kidney, and in cultures of vascular endothelial or smooth muscle cells, renal tubules and glomerular mesangium (Hamet et al 1984 Sato et al 1986b ; Stokes et al 1986). It is well known that ANP selectively dilates renal artery (Oshima et al 1984), and we have previously reported that the stimulatory effect of atriopeptin (AP) III on intracellular cGMP levels was greater in cultured vascular smooth muscle (VSM) cells from renal artery than those from mesenteric artery (Sato et al 1986b). Although these findings support the hypothesis that cGMP is a second messenger of the ANP action, the exact role of cGMP in these target cells or tissues remains to be clarified.…”