Annona muricata Ethanolic Leaf Extract Ameliorates Dexamethasone-induced Hypertension in Rats via Angiotensin-Converting Enzyme Inhibition, Sustained Systolic Blood Pressure Reduction and Renin-angiotensin System Modulation

Abstract

Hypertension is a major global health challenge and a leading risk factor for cardiovascular diseases. It is commonly associated with activation of the renin–angiotensin system (RAS), oxidative stress, and metabolic disturbances, which contribute to the progression of cardiovascular complications. This study evaluated the antihypertensive potential of ethanolic leaf extract of Annona muricata in dexamethasone-induced hypertensive rats and investigated its possible mechanisms of action through angiotensin-converting enzyme (ACE) inhibition, sustained systolic blood pressure (SBP) reduction, and modulation of the renin–angiotensin system. Hypertension was induced in experimental rats using dexamethasone. The animals were thereafter treated with varying doses of ethanolic leaf extract of Annona muricata, while a standard antihypertensive drug served as the positive control. Systolic blood pressure (SBP) was monitored using a non-invasive tail-cuff method. Biochemical analyses were conducted to determine ACE activity, oxidative stress markers, lipid profile, liver enzyme activities, electrolyte excretion, urine output, and haematological parameters. Histopathological examination of cardiac tissues was also performed to assess tissue integrity and possible protective effects of the extract. Dexamethasone administration significantly elevated SBP, ACE activity, oxidative stress markers, and lipid levels, confirming successful induction of hypertension. Treatment with the ethanolic leaf extract of Annona muricata produced significant and sustained reductions in SBP. The extract also significantly inhibited ACE activity, enhanced antioxidant status, reduced lipid peroxidation, and improved dyslipidemia. Increased electrolyte excretion and urine output suggested a notable diuretic effect. Furthermore, liver enzyme levels were normalised following treatment, while haematological parameters remained largely unchanged. Histopathological findings demonstrated the protective effects of the extract on cardiac tissues. The ethanolic leaf extract of Annona muricata exhibited significant antihypertensive activity in dexamethasone-induced hypertensive rats. The observed effects may be mediated through ACE inhibition, modulation of the renin–angiotensin system, antioxidant activity, and enhanced electrolyte excretion. These findings suggest that Annona muricata possesses promising therapeutic potential as a natural antihypertensive agent.