Abstract
BackgroundThe objective of the present study was to determine the effect of allisartan, a new angiotensin II type 1 receptor antagonist on vascular remodeling through voltage gated potassium channels (Kv7) in hypertensive rats.Methods The study included a total of 47 Sprague Dawley (SD) rats. The animals were randomized to sham operation (n = 14), untreated hypertensive control group (n = 18) and allisartan treatment group (n = 15). Using renal artery stenosis, hypertension was induced in animals. Single dose of allisartan was administered intra-gastrically to animals in the allisartan treatment group and match placebo in the other 2 groups. Wire myography was used to measure the muscle tension in isolated mesenteric arteries from the animals. Real-time polymerase chain reaction was used to quantify the expression of Kv7 channel mRNA subunits.ResultsAfter 4 weeks of treatment, a significant decrease in mean arterial, systolic and diastolic blood pressure (SBP and DBP) was observed in allisartan treatment group compared to hypertension control group. The median arterial wall thickness and area/diameter ratio reduced significantly in treatment group compared to untreated hypertension group (P < 0.05). Wire myography demonstrated increased relaxation of mesenteric artery with increase in concentration of ML213. A significant up-regulation in the expression of all Kv7 mRNA subunits was observed in allisartan group compared to untreated hypertension group.ConclusionsFrom the results, allisartan was found to lower BP and preserve vascular remodeling through Kv7 channels.
Highlights
The objective of the present study was to determine the effect of allisartan, a new angiotensin II type 1 receptor antagonist on vascular remodeling through voltage gated potassium channels (Kv7) in hypertensive rats
A significant increase in mean arterial, systoloc blood pressure (SBP) and diastolic blood pressure (DBP) was observed in hypertension group compared to sham group (P < 0.05) while a significant decrease in mean arterial, SBP and DBP was observed in allisartan treatment group compared to hypertension control group (P < 0.05)
A statistically significant difference was observed on comparing SBP of hypertension group Vs sham operation group (P < 0.0001) and allisartan treatment group Vs hypertension group (P < 0.0001) during all 4 weeks except for first week for allisartan treatment group Vs hypertension group (P = 0.8016)
Summary
The objective of the present study was to determine the effect of allisartan, a new angiotensin II type 1 receptor antagonist on vascular remodeling through voltage gated potassium channels (Kv7) in hypertensive rats. Zhang et al BMC Pharmacology and Toxicology (2021) 22:33 smooth muscle cells and neurons [9] It is reported as a major determinant of vascular tone [10]. Its action is mediated through AT1 receptors that are widely expressed in the kidneys especially in the smooth muscle cells of the arterioles [11]. Studies reported ARBs to be superior in ameliorating endothelial function and vascular damage [19,20,21]. Despite of their wide usage as first-line therapy, the cardiovascular protective effects of these agents still remained elusive [22]
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