Effects of obesity on the pharmacodynamics of nitroglycerin in conscious rats.
Literature reports have suggested that hemodynamic response toward organic nitrates may be reduced in obese patients, but this effect has not been studied. We compared the mean arterial pressure (MAP) responses toward single doses of nitroglycerin (NTG, 0.5-50 micro g) in conscious Zucker obese (ZOB), Zucker lean (ZL), and Sprague-Dawley (SD) rats. NTG tolerance development in these animal groups was separately examined. Rats received 1 and 10 micro g/min of NTG or vehicle infusion, and the maximal MAP response to an hourly 30 micro g NTG IVchallenge dose (CD) was measured. Steady-state NTG plasma concentrations were measured during 10 micro g/min NTG infusion. The Emax and ED50 values obtained were 33.9 +/- 3.6 and 3.5 +/- 1.7 micro g for SD rats, 33.2 +/- 4.1 and 3.0 +/- 1.4 micro g for ZL rats, and 34.8 +/- 3.9 and 5.3 +/- 2.8 micro g for ZOB rats, respectively. No difference was found in the dose-response curves among these 3 groups (P >.05, 2-way ANOVA). Neither the dynamics of NTG tolerance development, nor the steady-state NTG plasma concentrations, were found to differ among these 3 animal groups. These results showed that ZOB rats are not more resistant to the hemodynamic effects of organic nitrates compared with their lean controls. Thus, the acute and chronic hemodynamic effects induced by NTG are not sensitively affected by the presence of obesity in a conscious animal model of genetic obesity.
Wang
Ellen Q
EQ
Department of Pharmacokinetics, Dynamics, & Metabolism, Pfizer Global Research & Development, Eastern Point Road, MS4111, Groton, CT 06340, USA. ellen_q_wang@groton.pfizer.com
Fung
Ho-Leung
HL
D000704:Analysis of Variance; D000818:Animals; D008297:Male; D023421:Models, Animal; D005996:Nitroglycerin / Q000493:pharmacokinetics*; D009765:Obesity / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker
D005996:Nitroglycerin