Effects of late-onset and long-term captopril and nifedipine treatment in aged spontaneously hypertensive rats: Echocardiographic studies

Abstract

The purpose of the present study was to analyze the changes in blood pressure, left ventricular (LV) wall thickness and LV systolic function of aged spontaneously hypertensive rats (SHRs) either with or without antihypertensive therapy. Twenty-one SHRs aged 60.5±0.25 weeks were investigated over 22 weeks. They were divided into the following three groups (7 per group): untreated controls (CTRL), treatment with captopril (CAP, 60 mg kg(-1) daily) and treatment with captopril plus nifedipine (CAP+NIF, 60+10 mg kg(-1) daily). Systolic blood pressure (SBP) was regularly measured using the tail cuff method, and an echocardiogram was repeatedly obtained to examine the LV systolic and diastolic area, LV systolic fractional area change, cardiac output and LV myocardial wall thickness. Finally, heart catheterization was performed. While SBP remained stable in the CTRL animals over the experimental period, both of the antihypertensive treatments significantly reduced SBP by 20% in the treated animals (P<0.001). Echocardiography demonstrated that both the systolic and the diastolic LV function of the untreated SHRs deteriorated over time, whereas both types of antihypertensive treatments attenuated and delayed but did not completely prevent the decline in LV systolic function. Cardiac output, as determined by pulsed wave Doppler echocardiography, remained significantly higher in the treated animals than in CTRLs until week 20, but it then decreased. Heart catheterization showed a significant decrease in LV function, as reflected by the LV systolic pressure and contractility, in the CTRLs but not in treated animals. These findings clearly indicate that late-onset antihypertensive treatment with CAP or CAP+NIF is beneficial with respect to blood pressure reduction, LV hypertrophy attenuation and LV systolic function preservation.

How Effective Is a Late-Onset Antihypertensive Treatment? Studies with Captopril as Monotherapy and in Combination with Nifedipine in Old Spontaneously Hypertensive Rats

“…This corresponds to the functional effects of late-onset CAP and CAP + NIF treatments in old SHR as detected by echocardiography. Compared to untreated old SHR, both types of treatment significantly delayed the increase in LV wall thickness and preserved the systolic and diastolic pumping function for a significantly longer period of time [ 21 ].…”

“…This was also confirmed in an echocardiography study on old SHR. Both echocardiographic examination and heart catheterization showed marked LV dysfunction in untreated animals [ 21 ]. We assume that the loss in BW observed in the SHR CTRL group of the present study might be a consequence of this severe cardiac dysfunction.…”

Inhibition of the NFATc4/ERK/AKT Pathway and Improvement of Thiol-Specific Oxidative Stress by Dronedarone Possibly Secondary to the Reduction of Blood Pressure in an Animal Model of Ventricular Hypertrophy

“…Our results suggest that dronedarone produces inhibition of the NFATc4/ERK/AKT pathway and improvement of thiol-specific oxidative stress possibly secondary to the reduction of blood pressure. The SHR animal model has been used widely as an experimental model for LVH (Quintana-Villamandos et al, 2013;Zimmer et al, 2015;Lu et al, 2016;Zwadlo and Borlak, 2016;Salvetti et al, 2018). Ten-month-old male rats show a hypertension-related compensated LVH (Brooks et al, 2009).…”

Effect of Amlodipine and Captopril on Reproductive Capabilities of Male Laboratory Mice

“…2 While the Captopril is a commonly used antihypertensive drug. 26 That acts by inhibiting the activity of angiotensin-converting enzyme (ACE). 27 A zinc-containing metallopeptidase enzyme catalysing the conversion of angiotensin I into angiotensin II (a potent vasoconstrictor).…”