Biomedical subjects

Yasuhiro Nishimoto

Publications and source records attributed to Yasuhiro Nishimoto.

4 recordsLinked to original sources

PubMed2003

Inhibition of COX-2 prevents hypertension and proteinuria associated with a decrease of 8-iso-PGF2alpha formation in L-NAME-treated rats.

BACKGROUND: The inhibition of nitric oxide (NO) exerts injurious effects on the cardiovascular system by several mechanisms, such as the activation of the renin-angiotensin system, oxidative stress, and inflammatory cytokines. We examined whether COX-2, an inducible isoform of cyclooxygenase, is associated with the pathogenesis observed in N(omega)-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. METHODS: Three groups of 8-week-old male Sprague-Dawley rats were studied (n = 6 in each group): group 1, untreated controls; group 2, treated with L-NAME (1 g/l for 3 weeks, p.o.); and group 3, L-NAME co-treated with COX-2 inhibitor NS-398 (5 mg/kg per day, i.p.). The L-NAME-induced expression of COX-2 mRNA and protein was semi-quantified in the kidneys and the thoracic aorta. Urinary excretion of the prostaglandin 6-keto PGF(1alpha), thromboxane B2 (TXB2), and prostaglandin E2 (PGE2) was measured in the three groups. Moreover, urinary excretion of 8-iso-PGF(2alpha), a potent vasoconstricting arachidonic acid metabolite acting through thromboxane A (TXA) receptor activation, proposed recently as a marker of oxidative stress, was also measured. RESULTS: L-NAME induced significant increases in systolic blood pressure (P< 0.01), urinary protein (P< 0.05), and renal excretion of 8-iso-PGF(2alpha)(P< 0.01), compared with the control. In L-NAME-treated rats, the levels of COX-2 mRNA and protein were more than 50% higher in the kidneys (P< 0.05), and six-fold higher in the thoracic aorta (P< 0.01) than in control rats. NS-398 significantly ameliorated an increase in systolic blood pressure (P< 0.01) and urinary protein (P< 0.05) induced by L-NAME. CONCLUSIONS: These data indicate that an increase in COX-2 expression might have a hypertensive effect, partly associated with 8-iso-PGF(2alpha) formation in l-NAME-treated rats.

Animals↗

PubMed2002

Relaxant properties mediated by nitroglycerin in aortic coarctation hypertensive rats.

Nitroglycerin-mediated vasorelaxation is chiefly attributed to the cyclic guanosine monophosphate (cGMP)-dependent pathway, and partly to the cGMP-independent pathway via calcium-activated K(+) channels (K(Ca)). To investigate whether chronic hypertension alters responses of vascular smooth muscle to vasoactive agonists, we determined nitroglycerin-mediated relaxation of aortic rings from coarctation hypertensive rats. Banding the abdominal aorta above the renal arteries for 4 weeks elevated blood pressure and caused cardiac hypertrophy by 49%. In response to nitroglycerin, the relaxation of aortic rings precontracted with 10(-7) M norepinephrine was lower in the banded group than in the sham-operated group. Methylene blue, a guanylate cyclase inhibitor, suppressed a greater part of nitroglycerin-mediated relaxation and reached similar levels of relaxation in the two groups. Charybdotoxin, a specific K(Ca) channel blocker, also suppressed the relaxation by about 40% in the aortic rings from sham-operated animals, but not in those from the banded group. The response to charybdotoxin was markedly diminished or virtually eliminated in the banded group in the presence or absence of methylene blue. The combination of charybdotoxin and methylene blue nearly abolished nitroglycerin-mediated relaxation in the sham-operated group, whereas nitroglycerin-mediated relaxation was seen to remain in the banded group. These results indicate that the involvement of cGMP-independent K(Ca) channels in nitroglycerin-mediated relaxation disappeared after the development of hypertension produced by aortic coarctation.

Animals↗

PubMed2002

Decrease in renal medullary endothelial nitric oxide synthase of fructose-fed, salt-sensitive hypertensive rats.

We investigated the expression of endothelial NO synthase (eNOS) in the kidneys of fructose-fed insulin-resistant rats (FFR) with a low- or high-sodium diet. Male Sprague-Dawley rats were fed a control (C) or high-fructose (40% fructose; F) diet, with each coming in low-sodium (0.024% NaCl; LS-C or LS-F) or high-sodium (3% NaCl; HS-C or HS-F) varieties, for 2 weeks. Half of the FFR were orally administered pioglitazone (10 mg. kg(-1). day(-1)), an insulin-sensitizing agent (LS-FP or HS-FP). The systolic blood pressure was significantly higher in the HS-F rats than in the LS-F rats or the HS-C rats (HS-F rats, 129+/-4 mm Hg, versus LS-F rats, 115+/-3 mm Hg, P<0.05; or versus HS-C rats, 116+/-5 mm Hg, P<0.05), which indicated the salt dependence of hypertension in FFR. The protein expression of eNOS in the renal medulla of FFR was significantly lower than that in control rats during a high sodium load. The administration of pioglitazone prevented the hypertension (HS-F rats, 129+/-4 mm Hg, versus HS-FP rats, 113+/-3 mm Hg, P<0.05) and the reduction of medullary eNOS protein expression in HS-F rats. There was no significant difference in eNOS expression in the renal cortex or aorta between FFR and control rats, regardless of sodium load. These results suggest that the decrease in renal medullary NO production by eNOS during a high sodium load may play a role in fructose-fed, salt-sensitive hypertension.

Animals↗

PubMedDate not supplied

Quinapril treatment restores the vasodilator action of insulin in fructose-hypertensive rats.

1. Angiotensin-converting enzyme (ACE) inhibitors have been shown to improve insulin-resistance both experimentally and clinically. We therefore investigated the effects of quinapril, which has high tissue specificity for ACE, regarding the contribution of insulin to vascular contractions, as well as insulin sensitivity in a dietary rat model of insulin resistance. 2. Male Sprague-Dawley rats were divided into three groups: (i) rats fed normal chow (normal diet group); (ii) rats fed fructose-rich chow containing 40% fructose and 7% lard (fructose diet group); and (iii) rats fed fructose-rich chow plus quinapril (10 mg/kg per day; quinapril-treated group). 3. After 2 weeks, we evaluated systolic blood pressure, insulin sensitivity as assessed by steady state plasma glucose (SSPG) levels, response of aortic rings to phenylephrine (10-9 to 10-6 mol/L) in the presence or absence of insulin and the response of aortic rings to acetylcholine. 4. Feeding rats fructose-rich chow resulted in an elevation of blood pressure (P < 0.01) and SSPG levels (P < 0.01). Quinapril treatment significantly prevented increases in both blood pressure and SSPG, with a return to the levels seen in the normal diet group. 5. In the absence of insulin, the maximal contractile response to phenylephrine did not differ between the three groups. However, in the presence of insulin (100 mU/mL), the contractile response to phenylephrine (10-6 mol/L) was reduced by 22.8 +/- 1.2% in the normal diet group, although no insulin effects were observed in the fructose diet group (P < 0.01). Quinapril restored the inhibitory effect of insulin on phenylephrine-induced contractions. 6. In addition, the reduction in relaxation induced by acetylcholine in the fructose diet group was significantly reversed by quinapril treatment. 7. It is concluded that the fructose diet impairs the vasodilator effects of insulin as well as acetylcholine-induced relaxation in rat thoracic aortas. Quinapril prevented deterioration in the responses of the aortic rings, suggesting that ACE inhibitors may be useful for treating vascular insulin resistance.

Acetylcholine↗