Effect of Ivabradine on a Hypertensive Heart and the Renin-Angiotensin-Aldosterone System in L-NAME-Induced Hypertension

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.

Ivabradine reversed nondipping heart rate in rats with l‐NAME‐induced hypertension

“…In our previous experiment with l-NAME-induced hypertension, ivabradine did not modify the serum level of angiotensin II but reduced serum aldosterone concentration and systolic blood pressure. 16 We hypothesize that ivabradine may have different impact on the rennin-angiotensin-aldosterone system during the day and night, what might have been reflected in the different effect of ivabradine on HR during the daily and nocturnal period.…”

“…blood pressure, heart rate, hypertension, ivabradine, nondipping chosen according to previous animal experiments. [13][14][15][16] Rats were individually housed and maintained under standard laboratory conditions In controls after 4 weeks of the experiment, SBP night and SBP day were 126.9 ± 3.9 mm Hg and 117.9 ± 3.6 mm Hg, respectively ( Figure 1A,B); no night-to-day SBP dip-pattern was observed ( Figure 2A). HR night and HR day were 367.6 ± 9.4 bpm and 345.9 ± 6.2 bpm, respectively ( Figure 1C,D); and the night-to-day HR dip was 5.6 ± 1.8% ( Figure 2B).…”

“…Interestingly, in line with our previous results, both daytime-dosed and night-time-dosed ivabradine exerted an antihypertensive effect. 16,23 The irregular This indicates that nondipping BP might be considered inferior to nondipping HR regarding CV risk assessment. 3 The mechanisms behind the protective effect of ivabradine in terms of reversal the nondipping HR may be complex.…”

Morphological and Functional Characteristics of Animal Models of Myocardial Fibrosis Induced by Pressure Overload

“…e model is characterized by the stable increase of blood pressure and simple replication method [153]. A recent study has shown that elevated blood pressure caused by L-NAME may be affected by diet [154].…”

Uric Acid Level is Positively Associated With NT-proBNP Concentration in Slovak Heart Failure Patients

“…Therefore, research which is focused on finding new potential targets in the treatment of HF, is of the highest priority and heart remodeling and failure continuously attracts the attention of clinical and experimental cardiology (Lacko et al 2018, Cundrle et al 2018, Simko and Pechanova 2010, Simko et al 2018a, Simko et al 2018b.…”