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Contribution of nitric oxide produced by inducible nitric oxide synthase to vascular responses of mesenteric arterioles in streptozotocin‐diabetic rats
Author(s) -
Ishikawa Tomohisa,
Kohno Fumika,
Kawase Ryosuke,
Yamamoto Yuri,
Nakayama Koichi
Publication year - 2004
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705611
Subject(s) - phenylephrine , medicine , endocrinology , streptozotocin , nitric oxide synthase , nitric oxide , mesenteric arteries , arteriole , microcirculation , vasoconstriction , chemistry , diabetes mellitus , blood pressure , artery
The functional changes in mesenteric arterioles of streptozotocin‐induced diabetes were investigated by intravital microscopy. The mesentery was exteriorized from anesthetized rats, spread in a chamber, and superfused with Tyrode solution. All drugs tested were applied to the superfusing Tyrode solution. Compared with age‐matched controls, the diabetic rats showed enhanced vascular sensitivity to phenylephrine, an α 1 ‐adrenoceptor agonist. The preincubation of the mesentery with N G ‐nitro‐ L ‐arginine ( L ‐NNA), a nitric oxide synthase (NOS) inhibitor, shifted the phenylephrine‐concentration–response curves to the left in both the diabetic and control rats. Even in the presence of L ‐NNA, the sensitivity to phenylephrine was higher in the diabetic rats than in the control. Acetylcholine relaxed the mesenteric arterioles in both groups, but to a significantly greater extent in the control than in the diabetic rats. However, the L ‐NNA‐induced constriction of arterioles did not differ significantly between the groups. In contrast, the amplitude of the constrictions of mesenteric arterioles induced by S ‐ethylisothiourea, an inducible NOS (iNOS) inhibitor, was significantly greater in the diabetic rats than in the control. Immunostaining of the mesentery with a specific antibody for iNOS revealed iNOS in the microvessels of only the diabetic rats. These results suggest that constrictor responses to α 1 ‐adrenoceptor stimulation are sensitized in the mesenteric arterioles of STZ‐diabetic rats, and that iNOS expressed in the arteriolar smooth muscle plays a role in suppressing the basal tone and the reactivity of the arterioles in STZ‐diabetic rats.British Journal of Pharmacology (2004) 141 , 269–276. doi: 10.1038/sj.bjp.0705611