Abstract
Aliskiren, a renin inhibitor, has been shown to have cardioprotective and blood pressure (BP) lowering effects. We aimed to determine the effects of nanoparticle-loaded aliskiren on BP, nitric oxide synthase activity (NOS) and structural alterations of the heart and aorta developed due to spontaneous hypertension in rats. Twelve week-old male spontaneously hypertensive rats (SHR) were divided into the untreated group, group treated with powdered or nanoparticle-loaded aliskiren (25 mg/kg/day) and group treated with nanoparticles only for 3 weeks by gavage. BP was measured by tail-cuff plethysmography. NOS activity, eNOS and nNOS protein expressions, and collagen content were determined in both the heart and aorta. Vasoactivity of the mesenteric artery and wall thickness, inner diameter, and cross-sectional area (CSA) of the aorta were analyzed. After 3 weeks, BP was lower in both powdered and nanoparticle-loaded aliskiren groups with a more pronounced effect in the latter case. Only nanoparticle-loaded aliskiren increased the expression of nNOS along with increased NOS activity in the heart (by 30%). Moreover, nanoparticle-loaded aliskiren decreased vasoconstriction of the mesenteric artery and collagen content (by 11%), and CSA (by 25%) in the aorta compared to the powdered aliskiren group. In conclusion, nanoparticle-loaded aliskiren represents a promising drug with antihypertensive and cardioprotective effects.
Highlights
Hypertension or high blood pressure generally leads to heart attacks, heart failure, kidney disease, stroke, and death and is still a major global health concern
The aim of our study was to analyze the effect of polylactide acid (PLA) nanoparticle-loaded aliskiren on blood pressure, nitric oxide synthase activity, the vasoactivity of the mesenteric artery and structural alterations of the heart and aorta that developed due to spontaneous hypertension in rats
The discrepancies in obtained diameters are caused by the use of different sizing techniques with different physical principles, while scanning electron microscope (SEM) provides morphological information about nanoparticles and the consequent determination of size based on defined measures of diameter, dynamic light scattering (DLS) and differential centrifugal sedimentation (DCS) allow direct particle size analysis
Summary
Hypertension or high blood pressure generally leads to heart attacks, heart failure, kidney disease, stroke, and death and is still a major global health concern. There are many classes of antihypertensive drugs, which lower blood pressure by different means. Aliskiren is the most recent antihypertensive agent and acts by inhibition of renin, the first step in RAAS. Aliskiren binds to the S3bp binding site of renin, which is essential for its activity. By binding to this pocket, aliskiren prevents the conversion of angiotensinogen to angiotensin I [9]. This effect subsequently decreases the formation of angiotensin II, followed by a decrease in vasoconstriction, Molecules 2019, 24, 2710; doi:10.3390/molecules24152710 www.mdpi.com/journal/molecules
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