ReviewCritical insights into the beneficial and protective actions of the kallikrein-kinin system

Hypertension is characterized by an imbalance between the renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS). Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II AT-1 receptor antagonists (also known as sartans or ARBs) are potent modulators of these systems and are highly effective as first-line treatments for hypertension, diabetic nephropathies, and diseases of the brain and coronary arteries. However, these agents are mechanistically distinct and should not be considered interchangeable. In this mini-review, we provide novel insights into the often neglected roles of the KKS in the beneficial, protective, and reparative actions of ACEIs. Indeed, ACEIs are the only antihypertensive drugs that properly reduce the imbalance between the RAS and the KKS, thereby restoring optimal cardiovascular homeostasis and significantly reducing morbidity and the risk of all-cause mortality among individuals affected by hypertension and other cardiovascular diseases.Synopsis and bullet points
- Hypertension, a disease derived from an imbalance between two endogenous systems, the renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS)
- Effective mediators of these two systems include the octapeptide angiotensin II (Ang II) and the nonapeptide bradykinin (BK)
- Disease pathology involves an increase in peripheral resistance (↑PVR), an increase in cardiac output (↑CO), hypertrophy of the heart and peripheral vessels, and nephropathies.
- Preventive measures include a healthy diet, regular exercise, smoking cessation, and limiting salt and alcohol consumption.
- Rational therapy consists of drugs that aim not only to reduce blood pressure (BP) but also to decrease morbidity and mortality.
- The goal of therapy is to inhibit the RAS and potentiate the KKS, both of which can be achieved with ACE Inhibitors (ACEIs), thereby restoring optimal cardiovascular homeostasis.