The effect of an NO donor, pentaerythrityl tetranitrate, on biochemical, functional, and morphological attributes of cardiovascular system of spontaneously hypertensive rats

Abstract

Abstract. The status of nitric oxide (NO) in spontaneously hypertensive rats (SHR) is unclear and its bioavailability may be affected by imbalance with reactive oxygen species. We studied cardiovascular effects of an NO donor, pentaerythrityl tetranitrate (PETN) in SHR. We used Wistar rats, SHR and SHR treated with PETN (100 mg/kg/day). After six weeks, myocardium and aorta from each group were taken for biochemical and iliac artery for functional and morphological study. Long-term administration of PETN to SHR increased cGMP level in platelets and did not affect blood pressure. In myocardium, the therapy resulted in a decrease in cardiac hypertrophy and MDA level, and the increased antioxidant enzyme activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx). In aorta, PETN decreased the NO-synthase activity and had no affect on the enzyme activities of SOD and GPx or on MDA level. In the iliac artery, the endothelium-dependent relaxation to acetylcholine was slightly improved and the maximum vasoconstriction to noradrenaline was decreased. Wall thickness, cross-sectional area, inner diameter, and wall thickness/ inner diameter measured after perfusion fixation (120 mmHg) were not affected. The small effect of PETN on cardiovascular system suggests that NO deficiency is probably not the main cause of pathological alterations in SHR.

Maternal Treatment of Spontaneously Hypertensive Rats With Pentaerythritol Tetranitrate Reduces Blood Pressure in Female Offspring

“…Treatment of SHR with PETN (200 mg/kg per day by gavage) for 6 weeks does not change blood pressure. 22,23 Thus, the persistent blood pressure reduction in the female offspring is unrelated to the blood pressure of the parental animals. In other words, a blood pressure reduction in the parental animal is not necessary for the blood pressure-lowering effect in the offspring.…”

Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress

“…24 ) ( 65 , 253 , 278 ). The induction of extracellular SOD and GPx-1 ( 78 ) may represent another important intrinsic antioxidant pathway activated by PETN in vivo treatment ( 256 ) and may explain its beneficial effects in hyperlipidemia ( 124 , 165 ) and arterial hypertension ( 279 ).…”

Redox signaling in pathophysiology of hypertension

“…For the cell to maintain ROS homeostasis there is a delicate balance existing between the production and degradation of the radicals [88,89]. The later involves activation of SOD isoforms, which are the first natural antioxidant defense proteins that improve redox balance.…”