Diabetes-induced changes of nitric oxide influence on the cardiovascular action of secretin.
The modulation by condition of the lack or the excess of nitric oxide (NO) on cardiovascular action of secretin in diabetic rats was investigated. In vitro the isolated heart function and in vivo, the systolic (SBP), diastolic (DSP) blood pressure and heart rate (HR) were measured. Secretin evoked inotropic positive effect and increased coronary outflow (CO), in vivo did not increase systemic pressure and the highest dose of the peptide increased the heart rate. NO synthase inhibitor, N(G) nitro-L-arginine methyl ester (L-NAME) deeply increased the systemic pressure and in vitro decreased coronary outflow. L-arginine and sodium nitroprusside (SNP) did not influence the isolated heart function and in vivo decreased the systemic pressure. L-NAME preserved the inotropic positive effect of secretin and the increase of the coronary outflow. In vivo co-administration of L-NAME+secretin evoked hypotensive effect and abolished the increase of the heart rate after the highest dose of the peptide. L-arginine abolished inotropic positive effect of the peptide and the increase of coronary outflow. In vivo co-administration of these substances caused hypotension and attenuated the increase of the heart rate after the highest dose of secretin. Co-injection of SNP and secretin preserved the inotropic effect of secretin and abolished the increase of the coronary outflow. In vivo infusion of SNP+secretin evoked hypotension and similarly to L-arginine, SNP abolished tachycardia induced by the highest dose of secretin. Both the lack and the excess of nitric oxide changed the cardiovascular action of secretin in diabetic rats.
Sitniewska
Ewa Maria
EM
Department of Pharmacology, Medical Academy of Bialystok, 2c Mickiewicza: 15-222, Bialystok, Poland.
Wiśniewska
Róza Julia
RJ
Wiśniewski
Konstanty
K
D000818:Animals; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism*; D006439:Hemodynamics; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012633:Secretin / Q000494:pharmacology*
D012633:Secretin; D009599:Nitroprusside; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester