Abstract
Ivabradine, the selective inhibitor of the If current in the sinoatrial node, exerts cardiovascular protection by its bradycardic effect and potentially pleiotropic actions. However, there is a shortage of data regarding ivabradine’s interaction with the renin-angiotensin-aldosterone system (RAAS). This study investigated whether ivabradine is able to protect a hypertensive heart in the model of L-NAME-induced hypertension and to interfere with the RAAS. Four groups (n = 10/group) of adult male Wistar rats were treated as follows for four weeks: control, ivabradine (10 mg/kg/day), L-NAME (40 mg/kg/day), and L-NAME plus ivabradine. L-NAME administration increased systolic blood pressure (SBP) and left ventricular (LV) weight, enhanced hydroxyproline concentration in the LV, and deteriorated the systolic and diastolic LV function. Ivabradine reduced heart rate (HR) and SBP, and improved the LV function. The serum concentrations of angiotensin Ang 1–8 (Ang II), Ang 1–5, Ang 1–7, Ang 1–10, Ang 2–8, and Ang 3–8 were decreased in the L-NAME group and ivabradine did not modify them. The serum concentration of aldosterone and the aldosterone/Ang II ratio were enhanced by L-NAME and ivabradine reduced these changes. We conclude that ivabradine improved the LV function of the hypertensive heart in L-NAME-induced hypertension. The protective effect of ivabradine might have been associated with the reduction of the aldosterone level.
Highlights
Ivabradine is a novel selective inhibitor of hyperpolarization-activated cyclic nucleotide-gated channels, inducing heart rate (HR) reduction [1]
Since heart remodeling is associated with the activation of angiotensin II or aldosterone, we investigated whether the potential effects of ivabradine in L-NAME-hypertension are related to its interference with the renin-angiotensin-aldosterone system (RAAS)
Average systolic blood pressure (SBP) decreased by ivabradine treatment compared to the L-NAME group (Figure 1A)
Summary
Ivabradine is a novel selective inhibitor of hyperpolarization-activated cyclic nucleotide-gated channels, inducing heart rate (HR) reduction [1]. Ivabradine was shown to attenuate chemokine-induced migration of CD4-positive lymphocytes in vivo [4], reduce vascular nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in apolipoprotein E (ApoE)-deficient mice [5], improve the functioning of myocardial mitochondria in an infarcted pig heart [3], and reduce high-sensitivity C-reactive protein levels in patients with acute coronary syndrome [6]. As a result of these anti-inflammatory, antiapoptotic, and oxidative stress reducing actions, ivabradine improved the endothelial function in ApoE knockout mice [7]; attenuated systolic and diastolic dysfunction, left ventricular hypertrophy (LVH), and fibrosis in angiotensin II-induced HF in rats [8]; and exerted an antihypertrophic effect on the aorta in spontaneously hypertensive rats [9]. Data regarding the potential protection of ivabradine on a hypertensive heart are sparse
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