Increased inward rectifier K + current of coronary artery smooth muscle cells in spontaneously hypertensive rats; partial compensation of the attenuated endothelium‐dependent relaxation via Ca 2+ ‐activated K + channels

2019 ◽  
Vol 47 (1) ◽  
pp. 38-48
Author(s):  
Hae Jin Kim ◽  
Ming Zhe Yin ◽  
Suhan Cho ◽  
Sung Eun Kim ◽  
Seong Woo Choi ◽  
...  
1997 ◽  
Vol 273 (2) ◽  
pp. H647-H654 ◽  
Author(s):  
M. Cappelli-Bigazzi ◽  
S. Rubattu ◽  
C. Battaglia ◽  
R. Russo ◽  
I. Enea ◽  
...  

Hypercholesterolemia is associated with more rapid development of atherosclerosis, and hypertension is frequently associated with abnormal vascular function. Therefore, to investigate the role of hypercholesterolemia and hypertension on vascular function, we studied three groups of male rats (aged 6 wk): normotensive Wistar-Kyoto rats (WKY) as a control group and spontaneously hypertensive rats (SHR) receiving either standard diet (SD; SHR-SD) or high-cholesterol (1%) diet (ChD; SHR-ChD). Vascular reactivity was tested on isolated aortic rings at 4 wk and at 3 and 6 mo of diet. At 3 mo, endothelium-dependent relaxation to acetylcholine (ACh) and ADP was significantly reduced in SHR-ChD but not in SHR-SD compared with WKY. At 6 mo, relaxations to ACh were further impaired in both SHR groups compared with WKY. Endothelium-independent vasodilation to nitroglycerin (NTG) was not different in the three groups of animals throughout 6 mo of diet. In additional experiments, we evaluated vascular reactivity in rats fed with ChD enriched with an excess of vitamin D [atherogenic diet (AD)] capable of producing vascular atherosclerotic lesions. In particular, we studied three additional groups of WKY and SHR rats fed with SD, AD, or AD plus a nonhypotensive dose of the calcium antagonist nitrendipine (Nit). Vasodilation to ACh and ADP was significantly blunted in WKY-AD compared with WKY-SD, whereas it was partially improved in WKY-Nit. There were no differences in endothelium-independent relaxation to NTG in the three WKY groups. In contrast, SHR-AD showed a marked reduction of endothelium-dependent and -independent vasodilation, but only endothelium-dependent vasodilation was preserved by addition of Nit to the diet. These data suggest that the development of vascular dysfunction in rat genetic hypertension is accelerated by ChD, in absence of detectable vascular lesions. Our study also shows that AD alters both vascular smooth muscle and endothelium-dependent relaxation. Low doses of Nit partially preserve endothelium-dependent vasodilation but do not affect the impairment of smooth muscle function in these rats.


2018 ◽  
Vol 17 (4) ◽  
pp. 103-109
Author(s):  
A. V. Nosarev ◽  
Yu. G. Birulina ◽  
I. V. Petrova ◽  
I. V. Kovalev ◽  
S. V. Gusakova ◽  
...  

Aim.To study the ionic mechanisms which underlie regulation contractile activity of vascular smooth muscles and the erythrocytes membrane potential from spontaneously hypertensive rats.Materials and methods.The effect of acetylcholine (ACX), 10 μM, and Ca2+ -ionophore A23187, 10 μM, on the contractile reactions of isolated smooth muscle segments of the aorta from 11-week-old spontaneously hypertensive rats (SHR) and Wistar – Kyoto rats (WKY) induced by phenylephrine (PE), 1 μM, was measured by the mechanography. 11-week-old SHR were divided into control and experimental groups depending on the drug administration (amlodipine 10 mg/kg given intragastrically). Blood pressure (BP) in SHR was measured before and after treatment. The amplitude of the hyperpolarizating response (HO) and the activity of Ca2+-dependent K+-channels of the erythrocyte membrane of SHR were performed with potentiometric method.Results.In response to the stimulating effect of the ACX or the calcium ionophore A23187, the smooth muscle segments of the aorta from the WKY and SHR precontracted with PE were relaxed. To the addition of the ACX, the vascular segments of the SHR responded with a stronger dilatation than the WKY segments, but not the action of the Ca2+-ionophore. Treatment of SHR with blocker of Ca2+-channels of L-type amlodipine caused a decrease the BP, and an increase in the relaxing effect of intact aortic segments on the ACX and Ca2+-ionophore. There was an increase the amplitude of HO and activity of Ca2+-dependent K+-channels of the erythrocyte membrane from SHR.Conclusion.Relaxation of vascular smooth muscle in SHR is caused by changes in the endothelial function and Ca2+-dependent ionic conductivity of the myocyte membrane. An increase of the hyperpolarizating response of the erythrocyte membrane from rats with spontaneous hypertension is associated with activation of potassium channels. The selective effect on these intracellular targets can serve as a basis for the development of antihypertensive drugs.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Ana Arnalich-Montiel ◽  
María Carmen González ◽  
Emilio Delgado-Baeza ◽  
María Jesús Delgado-Martos ◽  
Luis Condezo-Hoyos ◽  
...  

The aim of this study was to assess the effects of short-term esmolol therapy on coronary artery structure and function and plasma oxidative stress in spontaneously hypertensive rats (SHR). For this purpose, 14-month-old male SHR were treated for 48 hours with esmolol (SHR-E, 300 μg/kg/min). Age-matched untreated male SHR and Wistar Kyoto rats (WKY) were used as hypertensive and normotensive controls, respectively. At the end of intervention we performed a histological study to analyze coronary artery wall width (WW), wall-to-lumen ratio (W/L), and media cross-sectional area (MCSA). Dose-response curves for acetylcholine (ACh) and sodium nitroprusside were constructed. We also assessed several plasma oxidative stress biomarkers, namely, superoxide scavenging activity (SOSA), nitrites, and total antioxidant capacity (TAC). We observed a significant reduction in WW (P<0.001), W/L (P<0.05), and MCSA (P<0.01) and improved endothelium-dependent relaxation (AUCSHR-E=201.2±33versusAUCSHR=97.5±21,P<0.05) in SHR-E compared with untreated SHR; no differences were observed for WW, MCSA, and endothelium-dependent relaxation by ACh at higher concentrations (10−6to 10−4 mol/l) for SHR-E with respect to WKY. SOSA (P<0.001) and nitrite (P<0.01) values were significantly higher in SHR-E than in untreated SHR; however, TAC did not increase after treatment with esmolol. Esmolol improves early coronary artery remodeling in SHR.


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