Korean J Physiol Pharmacol.  1999 Aug;3(4):375-382.

Enhanced expression of inducible nitric oxide synthase may be responsible for altered vascular reactivity in streptozotocin-induced diabetic rats

• Jang JK
• Kang YJ
• Seo HG
• Seo SJ
• Chang KC

Abstract

Growing evidence indicates that enhanced generation or actions of nitric oxide (NO) are implicated in the pathogenesis of hypertension in spontaneously hypertensive rats and diabetic nephropathy in streptozotocin (STZ)-induced diabetic rats. We investigated whether inducible nitric oxide synthase (iNOS) expression in STZ-induced diabetic rats is responsible for the alterations of vascular reactivity. Diabetic state was confirmed 28 days after injection of STZ (i.p) in rats by measuring blood glucose. In order to evaluate whether short term (4 weeks) diabetic state is related with altered vascular reactivity caused by iNOS expression, isometric tension experiments were performed. In addition, plasma nitrite/nitrate (NOx) levels and expression of iNOS in the lung and aorta of control and STZ-treated rats were compared by using Griess reagent and Western analysis, respectively. Results indicated that STZ-treated rats increased the maximal contractile response of the aorta to phenylephrine (PE), and high K+, while the sensitivity remained unaltered. Endothelium-dependent relaxation, but not SNP-mediated relaxation, was reduced in STZ-treated rats. Plasma nitrite/nitrates are significantly increased in STZ-treated rats compared to controls. The malondialdehyde (MDA) contents of liver, serum, and aorta of diabetic rats were also significantly increased. Furthermore, nitrotyrosine, a specific foot print of peroxynitrite, was significantly increased in endothelial cells and smooth muscle layers in STZ-induced diabetic aorta. Taken together, the present findings indicate that enhanced release of NO by iNOS along with increased lipid peroxidation in diabetic conditions may be responsible, at least in part, for the augmented contractility, possibly through the modification of endothelial integrity or ecNOS activity of endothelium in STZ-diabetic rat aorta.

Keyword

Nitric oxide; Diabetes; Streptozotocin; Vascular smooth muscle; Peroxynitrite

MeSH Terms

Animals
Aorta
Blood Glucose
Diabetic Nephropathies
Endothelial Cells
Endothelium
Foot
Hypertension
Lipid Peroxidation
Liver
Lung
Malondialdehyde
Muscle, Smooth
Muscle, Smooth, Vascular
Nitric Oxide
Nitric Oxide Synthase Type II*
Peroxynitrous Acid
Phenylephrine
Plasma
Rats*
Rats, Inbred SHR
Relaxation
Streptozocin
Blood Glucose
Malondialdehyde
Nitric Oxide
Nitric Oxide Synthase Type II
Peroxynitrous Acid
Phenylephrine
Streptozocin