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Nitric oxide bioavailability is also regulated by the CGMP pathway in L‐NAME hypertensive cardiomyopathy of rats
Author(s) -
FerreiraMelo S.,
YugarToledo J. C.,
Souza W. A.,
Thomaz A. J.,
Franchini K. G.,
Coelho O. R.,
Lucca I.,
Moreno H.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.047
Subject(s) - sildenafil , bioavailability , nitric oxide , medicine , cardiomyopathy , pharmacology , pharmacokinetics , oral administration , phosphodiesterase , endocrinology , chemistry , heart failure , biochemistry , enzyme
Cardiac hypertrophy and large areas of perivascular and myocardial fibrosis characterize the hypertensive cardiomyopathy induced by NO biosynthesis inhibition (HC‐NOI) in rats. However, the pathophysiology of these alterations is still not fully clear. For example, the role of cGMP degradation by phosphodiesterase 5 (PDF 5) on this animal model remains unknown. To investigate the participation of the cGMP pathway in the NO bioavailability in this animal model of hypertension using sildenafil citrate as a pharmacological tool. Male Wistar rats (10‐12/group) received oral drugs administration: 1‐CONTROL (water ad libidum); 2‐ L‐NAME (65 mg/kg/day); 3‐ L‐NAME (65 mg/kg/day) + Sildenafil (45 mg/kg/day); 4– Sildenafil (45 mg/kg/day). After 8 weeks, the animals were sacrificed and the heart was removed. The heart weight index (HWI, mg/g) and the left ventricular weight index (LVWI, mg/g) were calculated. Fibrotic areas was evaluated by optical microscopy. Table below summarizes data at 8 th week: The development of the HC‐NOI in rats involves the cGMP pathway degradation. Clinical Pharmacology & Therapeutics (2004) 75 , P13–P13; doi: 10.1016/j.clpt.2003.11.047Control L‐NAME Sildenafil + L‐NAME SildenafilBody Weight (g) 382 ± 12 343 ± 11 347 ± 7 356 ± 7TCP (mmHg) 135 ± 11 179 ± 17 * 151 ± 9 # 129 ± 11HWI (mg/g) 2.96 ± 0.09 3.13 ± 0.04 * 2.87 ± 0.03 # 2.98 ± 0.06LVWI (mg/g) 1.79 ± 0.03 2.28 ± 0.14 * 1.97 ± 0.07 # 1.85 ± 0.03Fibrotic Areas (%) 7.5 ± 0.3 44.4 ± 2.6 * 24.4 ± 2.0 # 10.4 ± 1.5cGMP (ρmol/ml) 4.89 ± 0.32 2.93 ± 0.34 * 4.43 ± 0.23 # 6.03 ± 0.28 ** vs . Control Group ( P <0,05). # vs . L‐NAME Group ( P <0,05).