cyclic-gmp and 5-carboxamidotryptamine

In isolated Tyrode-perfused rat kidneys, the release of the cyclic nucleotides cAMP and cGMP was measured in response to several vasodilators, including nitric oxide (NO). During vasoconstrictions induced by methoxamine, a basal release of both cyclic nucleotides was detected in the renal effluent (357 +/- 32 fmol/min for cGMP and 3097 +/- 219 fmol/min for cAMP). Injection of acetylcholine (ACh; 11 nmol), sodium nitroprusside (SNP; 0.8 nmol) and atrial natriuretic factor (ANF; 80 pmol) caused a marked release of cGMP. The cGMP release induced by ACh was not altered by indomethacin (3 microM) but was markedly reduced by the NO synthase inhibitor nitro-L-arginine (L-NNA; 200 microM). Authentic NO (0.16-80 nmol) caused dose-dependent vasodilatations that were accompanied by increases in the overflow of cGMP. The vasodilatations caused by forskolin (6 nmol) and prostacyclin (PGI2; 3-52 nmol) were not accompanied by an overflow of cGMP. The vasodilator responses to 5-hydroxytryptamine (5-HT; 0.25-2 mumol), obtained in presence of the 5-HT2 receptor blocker ritanserin (10 nM) and the 5-HT3 blocker ICS 205930 (10 nM), were markedly reduced by L-NNA; however, they were not accompanied by the renal release of cGMP. Both forskolin and PGI2 induced the release of cAMP from perfused rat kidneys; ACh, 5-HT and 5-carboxamidotryptamine (5-CT) also evoked a significant release of cAMP into the renal effluent. The release of cAMP induced by ACh and 5-HT was reduced by indomethacin and L-NNA. Higher doses of NO released cAMP from the perfused rat kidneys. Our data illustrate that both cAMP and cGMP can be released by vasodilator substances into the venous effluent of isolated perfused rat kidneys. The dilator responses to 5-HT were sensitive to the NO synthase inhibitor L-NNA and were accompanied by the release of cAMP and not by the release of cGMP. Our data suggest that the dilator responses may be due to NO released from endothelial cells, which then activates adenylyl cyclase either directly or indirectly.

Topics: Acetylcholine; Animals; Atrial Natriuretic Factor; Citrulline; Colforsin; Cyclic AMP; Cyclic GMP; Epoprostenol; Kidney; Male; Methoxamine; Muscle, Smooth, Vascular; Nitric Oxide; Nitroprusside; Rats; Rats, Wistar; Serotonin; Vasoconstriction; Vasodilation; Vasodilator Agents