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The role of angiotensin -1 receptors in vasodilator responses of middle cerebral arteries in Sprague- Dawley rats

Questions: This study aimed to evaluate the role of angiotensin 1 receptors in endothelium-dependant (flow-induced dilation (FID) and acetylcholine (ACh)) and endothelium-independent (sodium nitroprusside ; SNP) vasodilator responses in cerebral resistance vessels of Sprague-Dawley rats. Additionally, the effects of AT-1R blockade on oxidative status and the role of oxidative stress on vasodilator responses was examined. Methods: Healthy male Sprague-Dawley rats (N=6-7 per group) were fed low salt (0.4%NaCl ; LS group) or LS+losartan (AT-1R blocker ; losartan 40 mg/day in water ad lib) for 7 days. Middle cerebral arteries’ responses to ACh (10-6M), SNP (10-6M) and FID (FID established by increases in pressure gradient (Δ10- Δ100 mmHg)) were studied in absence/presence of superoxide scavenger, TEMPOL (100 μmol/l). Plasma angiotensin II (ANG II) levels were measured by ELISA and plasma antioxidant capacity (FRAP) and lipid peroxidation level (TBARS) were measured by spectrophotometry. Mean arterial blood pressure (MAP) was also measured. Results: LS+losartan group exhibited significantly decreased vasodilation in response to ACh and FID, while SNP-induced dilation was preserved in both groups. FID was restored by addition of TEMPOL in chamber bath. LS+losartan group had significantly higher ANGII plasma concentration, higher TBARS and lower MAP compared to LS group. FRAP was similar between the groups. Conclusions: Increased oxidative stress may be underlying impaired endothelium-dependant dilation responses. Results suggest important role of ANG II in maintaining arterial relaxation responses via AT-1 receptor activation in physiological conditions. Support: Croatian Science Fundation grant #IP-2014- 09-6380.

high salt diet, angiotensin II type 1 receptor, oxidative stress, losartan

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