Endothelial triple-pathway vasorelaxation as an adjunctive strategy in resistant hypertension - PubMed
4 hours ago
- #chronic kidney disease
- #resistant hypertension
- #endothelial dysfunction
- Resistant hypertension (RH) affects 10-15% of treated hypertensive adults and up to 50% of individuals with chronic kidney disease (CKD).
- RH is defined by persistent high blood pressure despite multidrug therapy, leading to increased cardiovascular risks and high healthcare costs.
- Chronic endothelial dysfunction and maladaptive microvascular remodelling are key contributors to RH, especially in CKD-associated cases.
- The vascular endothelium regulates arterial tone through three vasodilatory systems: nitric oxide (NO), prostacyclin (PGI2), and endothelium-dependent hyperpolarization (EDH).
- Human tissue kallikrein-1 (KLK1) and its recombinant analogue, rinvecalinase alfa (DM199), show promise in restoring endothelial function by stimulating NO, PGI2, and EDH pathways.
- Phase II clinical trials with DM199 in CKD populations demonstrate blood pressure reduction, renal function stabilization, and reduced albuminuria.
- KLK1 therapy offers a favourable safety profile and potential benefits for CKD-associated RH where standard therapies often fail.