Effect of the structural modification of Candesartan with Zinc on hypertension and left ventricular hypertrophy

Area of Science:

• Pharmacology
• Cardiovascular Medicine
• Medicinal Chemistry

Background:

• Hypertension is a primary cause of left ventricular hypertrophy and heart failure.
• Candesartan is an angiotensin receptor antagonist used for hypertension.
• Structural modification of candesartan using Zinc (ZnCand) was explored to enhance its properties.

Purpose of the Study:

• To investigate the improved pharmacological properties of ZnCand compared to candesartan.
• To evaluate the antihypertensive and cardiac effects of ZnCand in vivo.

Main Methods:

• In vitro assessment of ZnCand's interaction with the AT1 receptor, oxidative stress, and calcium flux.
• In vivo treatment of spontaneously hypertensive rats (SHR) with ZnCand.
• Echocardiography, histology, and molecular marker analysis (BNP, CTGF, MMP-2) to assess cardiac hypertrophy and redox status.

Main Results:

• ZnCand showed stronger AT1 receptor interaction, reduced oxidative stress and calcium flux.
• ZnCand significantly decreased systolic blood pressure in SHR after 8 weeks.
• Cardiac hypertrophy markers, collagen content, and specific gene expressions were reduced by ZnCand, which also restored redox status.

Conclusions:

• Complexation with Zinc(II) enhances the antihypertensive efficacy of candesartan.
• ZnCand demonstrates significant cardioprotective effects by reducing cardiac hypertrophy and improving redox balance.
• This study highlights ZnCand as a potentially superior therapeutic agent for hypertension and associated cardiac complications.