Therapeutic development for hypertension by targeting the peptide-mediated blood pressure control

Blood pressure (BP) is controlled by coordinated actions of the neural, hormonal, renal, and vascular systems. Several endogenous peptides, such as angiotensin II (AngII), endothelin-1 and natriuretic peptides, which are usually generated from precursor proteins by enzymatic cleavage, are crucial to regulate the systems. Dysregulation of these tightly organized systems leads to hypertension and related diseases. Conventional anti-hypertensive therapies often fail to control hypertension or suppress hypertension-related pathologies, highlighting the need for novel therapeutic agents for managing hypertension. Both endogenous and exogenous peptides are highly selective to their targets and have adjustable pharmacokinetics, low toxicity, and weak immune responses. These characteristics may prove beneficial when investigating potential peptide-based anti-hypertensive medicine. Recent studies from our and other research groups have challenged and proposed newly identified peptides, artificially designed peptides, and peptidases that catalyze the vasoconstrictor peptide hormone AngII. These agents have all been shown to reduce BP in hypertensive animal models. In this review article, we have summarized these findings with the aim to promote understanding of the effects of peptides and peptidases on BP control. These data suggest that further development of innovative anti-hypertensive drugs may be productive.