Effect of nitric oxide inhibition on secretion of atrial natriuretic factor in isolated rat heart.
In addition to stretch, some hormones and neurotransmitters influence atrial natriuretic factor (ANF) secretion from the mammalian heart. In the present study, we investigated the effect of specific inhibition of nitric oxide/endothelium-derived relaxing factor (NO/ EDRF) on release of ANF from the isolated spontaneously beating heart during basal conditions and in response to arginine vasopressin (AVP; 3 x 10(-8) M), acetylcholine (ACh; 10(-6) M), and angiotensin II (ANG II; 4 x 10(-7) M) to determine whether NO is involved as a mediator of basal and hormone-modulated secretion of ANF. Basal secretion from control hearts remained stable for the duration of the experiment. Intracoronary perfusion of the heart with AVP, ACh, and ANG II reduced ANF secretion significantly by 58 +/- 4, 51 +/- 6, and 26 +/- 8%, respectively, independently of concomitant changes in coronary flow and heart rate. The NO donor sodium nitroprusside (SNP, 10(-4) M) inhibited ANF secretion comparably to AVP and ACh. The effect of SNP was not affected by inhibition of NO synthase activity with NG-nitro-L-arginine methyl ester (L-NAME; 3 x 10(-5) M). Similarly, L-arginine, (3 x 10(-4) M) but not its stereoisomer D-arginine (3 x 10(-4) M), significantly reduced ANF secretion. Subsequent perfusion with AVP singly or in combination with L-arginine or D-arginine did not affect ANF secretion further. The inhibitor of NO synthase NG-monomethyl-L-arginine (L-NMMA, 3 x 10(-5) M) did not affect basal secretion, but prevented the inhibitory effect of AVP and ACh. The effect of ANG II was not changed by L-NMMA. These results indicate that AVP and ACh inhibit ANF secretion in the isolated heart indirectly by stimulating NO/EDRF and suggest a novel function of NO/EDRF as a negative modulator of ANF secretion.
Melo
L G
LG
Department of Physiology, University of Toronto, Ontario, Canada.
Sonnenberg
H
H
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019323:omega-N-Methylarginine / Q000494:pharmacology
C472610:atrial natriuretic peptide, rat; D000804:Angiotensin II; D001127:Arginine Vasopressin; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester