Cmpd17b treatment for 28 days reduced mean arterial pressure by 6 mmHg in hypertensive BPH/2J mice and attenuated renovascular fibrosis.
Does Cmpd17b reduce blood pressure and reverse renovascular remodeling in a mouse model of established neurogenic hypertension?
Formylpeptide receptor agonism with Cmpd17b lowers blood pressure and reverses renovascular fibrosis in established neurogenic hypertension, highlighting inflammation-resolution pathways as a potential disease-modifying therapy.
Mean Difference: 6
Inflammation and sympathetic overactivity contribute to end-organ injury associated with hypertension. We previously demonstrated that targeting formylpeptide receptors (FPRs), which regulate and resolve inflammation, prevents cardiovascular damage in preclinical hypertension. Here, we investigated whether the FPR agonist Cmpd17b can reverse renovascular remodeling in established essential hypertension. Adult blood-pressure-normal (BPN/3 J) and high (BPH/2 J) mice received Cmpd17b (50 mg/kg/day, i.p.) for 28 days, with continuous blood-pressure monitoring via radiotelemetry. Cardiac and vascular function were assessed via ultrasonography, and structural remodeling in the left ventricle, kidney, and vasculature was quantified, with RNA sequencing. Cmpd17b selectively reduced blood pressure in BPH/2 J mice and improved aortic distensibility without altering cardiac function. Cmpd17b reduced collagen deposition across organs, most prominently in the kidney. RNA sequencing revealed kidney-specific upregulation of Serpina1e and Igfbp2, normalized by Cmpd17b. These findings identify FPR agonism as a promising therapeutic strategy for lowering blood pressure and reversing renovascular fibrosis. Formylpeptide receptor agonism with Compound 17b lowers blood pressure, restores vascular function, and reverses renovascular fibrosis in established hypertension, highlighting inflammation-resolution pathways as a promising disease-modifying therapy for hypertensive organ damage.
Singh et al. (Thu,) conducted a other in Neurogenic hypertension (n=26). Cmpd17b vs. Vehicle was evaluated on Mean arterial pressure (MAP) (reduced by 6 mmHg). Cmpd17b treatment for 28 days reduced mean arterial pressure by 6 mmHg in hypertensive BPH/2J mice and attenuated renovascular fibrosis.