Synergistic neuroprotective effects of combined treatment with olmesartan plus azelnidipine in stroke-prone spontaneously hypertensive rats

2014 ◽  
Vol 92 (10) ◽  
pp. 1330-1337 ◽  
Author(s):  
Yoshio Omote ◽  
Kentaro Deguchi ◽  
Syoichiro Kono ◽  
Wentao Liu ◽  
Tomoko Kurata ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Combined Treatment ◽  
Hypertensive Rats ◽  
Neuroprotective Effects ◽  
Spontaneously Hypertensive

Abstract 567: Combined Treatment With Irbesartan and Vitamin D Retards Renal Injury in Salt-loaded Uni-nephrectomized Stroke-prone Spontaneously Hypertensive Rats

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Tsuneo Takenaka ◽  
Tsutomu Inoue ◽  
Yoichi Ohno ◽  
Takashi Miyazaki ◽  
Akira Nishiyama ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vitamin D ◽  
Renal Injury ◽  
Spontaneously Hypertensive Rats ◽  
Combined Treatment ◽  
Prostaglandin F2α ◽  
Renin Angiotensin System ◽  
Immunoblot Analysis ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Vitamin D diminishes renin expression. In addition, we previously reported that vitamin D increased renal expression of klotho in rats with normal kidney function. In the present study, effects of vitamin D on renal injury was assessed in four groups of rats (n=6-8 for each group); uni-nephrectomized stroke-prone spontaneously hypertensive rats fed high salt (6%) diet as a control (C), those treated with irbesartan (100 mg/kg/day) (I), rats treated with calcitriol (30 ng/kg/day) (V), and rats treated with both irbesartan and calcitriol (I+V). Six weeks later, rats were killed with over-anesthesia, and harvested right kidney for analysis. As shown in table, systolic blood pressure (SBP) in C (p<0.05) was higher than I and I+V groups. While renal angiotensin II (AngII) concentration was lower in I and I+V groups than C, plasma AngII levels of I and V groups are higher and lower than C (p<0.05), respectively. In addition, urine albumin/creatinine ratio (Alb/Cr) was lower in I and I+V group than C, and 8-epi-prostaglandin F2α (PGF2α) excretion was reduced in V and I+V groups (p<0.05). Immunoblot analysis revealed that compared to C, renal klotho expression was preserved in V and I+V group (p<0.05). Creatinine clearance (Ccr) was elevated in I+V group than C. The present data indicate that irbesartan effectively decreases blood pressure with reductions in renal AngII and albuminuria. Our findings demonstrate that vitamin D enhances klotho expression, suppressing oxidative stress and albuminuria without substantial changes in renal AngII. The current results may provide evidence that renal renin-angiotensin system is regulated independently of circulating one.

Differential participation of calcium-activated potassium channel in endothelium-dependent hyperpolarization-type relaxation in superior mesenteric arteries of spontaneously hypertensive rats

2018 ◽  
Vol 96 (8) ◽  
pp. 839-844
Author(s):  
Makoto Ando ◽  
Takayuki Matsumoto ◽  
Shota Kobayashi ◽  
Maika Iguchi ◽  
Kumiko Taguchi ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Combined Treatment ◽  
Mesenteric Arteries ◽  
Hypertensive Rats ◽  
Α Subunit ◽  
Spontaneously Hypertensive ◽  
The Difference ◽  
Wistar Kyoto ◽  
Calcium Activated Potassium Channel ◽  
Relationship Of

The purpose of this study was to determine the relationship of KCa channels to endothelium-dependent hyperpolarizing factor (EDHF)-mediated relaxation induced by acetylcholine (ACh) in the superior mesenteric arteries of 7-month-old spontaneously hypertensive rats (SHR). Upon inhibition of nitric oxide synthase and cyclooxygenase, ACh-induced EDHF-mediated relaxation was found to be weaker in SHR than in age-matched Wistar Kyoto rats (WKY). These relaxations in both group were attenuated by combined treatment with small-conductance and intermediate-conductance Ca2+-activated K+ channels (SKCa and IKCa) inhibitors, with the exception of relaxation resistant to inhibition of these channels in SHR (vs. WKY). Treatment with large-conductance Ca2+-activated K+ channels (BKCa) inhibitor specifically attenuated relaxation in SHR, but not in WKY. Protein expression of IKCa and SKCa in the arteries did not differ between the 2 groups, whereas ratio of sloβ1 subunit to α subunit of BKCa was increased in SHR (vs. WKY). These results suggest that EDHF-mediated relaxations in superior mesenteric arteries are impaired in SHR, and utilize components of BKCa in addition to SKCa/IKCa channel activities, that the increased participation of BKCa may be attributable to alterations in α and sloβ1 subunit ratio, and that components unrelated to KCa activity may also contribute to the difference between SHR and WKY arteries.

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