cGMP Accumulation and Gene Expression of Soluble Guanylate Cyclase in Human Vascular Tissue

Gene expression of soluble guanylate cyclase (sGC) and cGMP accumulation in response to sodium nitroprusside (SNP) were studied in cultured human vascular cells and freshly harvested vascular tissue. As revealed by reverse transcriptasepolymerase chain reaction, cultured smooth muscle and endothelial cells, as well as freshly isolated human vascular tissue, express mRNA for the a, and p3 subunits but not for the a2 or p2 sGC. In cultured human cells, expression of the a3 and p3 subunits is evident even in the absence of increased cGMP accumulation in response to SNP. cGMP accumulation in cultured human cells from different vascular beds typically increased two- to fivefold (maximum of 1 1.4-fold) over baseline following stimulation with 100 pM SNP. Bovine, murine, canine, and avian vascular smooth muscle cells accumulated similar or lower amounts of cGMP than human cells, whereas porcine, rat, and rabbit smooth muscle cells accumulated greater amounts of cGMP. In freshly harvested human vessels, cGMP accumulation in response to SNP was found to increase fifteenfold over baseline. In contrast to the SNP-induced cGMP accumulation, cGMP levels in response to the particulate guanylate cyclase activator atriopeptin II were equal or greater in cultured human cells than in fresh human vascular tissue. We conclude that human vascular cells (fresh and cultured) express the mRNA for both a large (a,) and a small (p3) sGC subunit and that fresh human cells are more sensitive to SNP stimulation. o 1996 Wiley-Liss, Inc.