Ongoing Research into New High Blood Pressure Drugs
Understanding Blood Pressure
Blood pressure is defined as the force exerted by circulating blood on the walls of arteries. It comprises two measurements: systolic pressure, which occurs when the heart contracts, and diastolic pressure, which occurs during heart relaxation. Maintaining adequate blood pressure is crucial for delivering oxygen and nutrients to vital organs. This pressure fluctuates based on various situations; for instance, it temporarily rises during exercise before returning to a resting level. The body employs a complex network of nerves and hormonal feedback systems to regulate blood pressure as needed. Current medical guidelines recommend that resting blood pressure should remain below 120/80 mmHg. Research indicates that elevated resting blood pressure, despite being asymptomatic in the short term, significantly increases the risk of heart disease, stroke, and kidney failure over time.
Prevalence of High Blood Pressure
Hypertension, commonly referred to as high blood pressure, affects approximately one-third of adults globally and is a leading cause of premature death. In most cases, the underlying cause of hypertension remains unknown. However, several risk factors have been identified, including family history, high-salt diets, sedentary lifestyles, obesity, smoking, and advancing age. While modifying these risk factors can help reduce blood pressure, many individuals with hypertension will require medication.
Current Antihypertensive Treatments
Antihypertensive medications target the body’s mechanisms for controlling blood pressure. Despite the variety of available treatments, hypertension remains inadequately managed worldwide. This may be attributed to patients not adhering to prescribed medication regimens, as well as the complexity of hypertension’s underlying mechanisms. There is a pressing need for innovative therapies that address diverse blood pressure control pathways.
Recent Advances in Antihypertensive Drugs
Experts from the University of Paris, France, have reviewed recent developments in antihypertensive medications in the journal *Hypertension*.
Drugs for Heart Failure and Diabetic Kidney Disease
Developing new antihypertensive therapies is a challenging and expensive endeavor, requiring extensive long-term testing. However, some medications originally designed for other conditions, such as heart failure and diabetic kidney disease, have demonstrated blood pressure-lowering effects and are being explored for hypertensive patients.
Neprilysin Inhibitors
These inhibitors enhance hormonal feedback systems that promote vasodilation and sodium excretion in the kidneys. Originally developed for heart failure treatment, when combined with angiotensin receptor inhibitors, they show potential as antihypertensives. Preliminary clinical trials of the combination drug sacubitril/valsartan indicate safety and effectiveness for short-term hypertension treatment, although no long-term trials specifically in hypertensive patients are currently planned.
Soluble Guanylate Cyclase (sGC) Stimulators
sGC stimulators play a role in various cardiovascular functions, notably promoting vasodilation. Currently undergoing clinical trials for heart failure, they have shown promise in animal studies for reducing blood pressure. However, trials in heart failure patients have not demonstrated significant blood pressure changes, necessitating further investigation into their antihypertensive potential.
Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors
These inhibitors facilitate glucose excretion in urine and are primarily used to treat type 2 diabetes. They have shown beneficial cardiovascular effects, particularly in reducing heart failure risk among diabetic patients. While the exact mechanisms remain unclear, SGLT2 inhibitors appear to lower blood pressure and may be advantageous for hypertensive diabetic patients.
Innovative Approaches in Antihypertensive Treatment
A deeper understanding of cardiovascular control pathways in the brain has led to the development of novel antihypertensive therapies. Centrally acting aminopeptidase A inhibitors work within the brain to inhibit neural and hormonal pathways that elevate blood pressure. Initial studies on the aminopeptidase inhibitor firabastat have yielded promising results, though larger comparative trials are warranted.
Endothelins, hormones produced by arterial lining cells, play a role in constricting blood vessels and raising blood pressure. Overproduction of endothelins is linked to hypertension and vascular diseases. Endothelin receptor antagonists (ERAs), designed to block these effects, have been studied for hypertension treatment but have faced challenges due to severe side effects. More selective ERAs are being explored for patients with resistant hypertension that conventional medications fail to control.
Importance of Personalized Treatment Programs
While promising new antihypertensive drugs are in development, evaluating their efficacy and safety will take time. In the interim, creating personalized treatment plans using existing medications, enhancing adherence to treatment, improving healthcare access, and reducing drug costs are critical steps in addressing the challenges of uncontrolled and resistant hypertension.
Conclusion
Research into new antihypertensive therapies continues to evolve, addressing the complex nature of hypertension and the need for effective management strategies.
Author Information
Written by Julie McShane, MA MB BS
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Reference
Azizi M., Rossignol P., Hulot J-S. Emerging drug classes and their potential use in hypertension. *Hypertension* 2019:74:1075-1083.