Soluble guanylate cyclase stimulators and activators as potential antihypertensive drugs

Poor blood pressure control in treated patients with hypertension is an important topic in the field of hypertension, and an unmet need for new therapeutic drugs remains. Soluble guanylate cyclase (sGC), a key signal transduction enzyme responsible for vasodilation, has attracted increasing interest as a therapeutic target in various cardiovascular diseases. Two different sGC agonists, sGC stimulators and activators, can increase its enzymatic activity in reduced and oxidized/apo forms, respectively. With some sGC agonists being already in clinical use, drugs in this category are expected to become new therapeutic agents for various conditions, including hypertension. In this review, we summarize the current knowledge on the antihypertensive effects of sGC agonists in various preclinical studies involving animal models of spontaneous hypertension, salt-sensitive hypertension, nitric oxide-deficient hypertension, renin-angiotensin-aldosterone system-dependent hypertension, malignant hypertension, metabolic syndrome, renoprival hypertension, renovascular hypertension, drug-induced hypertension, pregnancy hypertension, and treatment-resistant hypertension. Our compilation provides a comprehensive rationale for advancing the clinical development of sGC agonists for the treatment of hypertension.