Antihypertensives: Mechanism-Based Comparison

Antihypertensive agents lower blood pressure through distinct mechanisms targeting different components of the cardiovascular system. ACE inhibitors (lisinopril, enalapril) block angiotensin-converting enzyme, preventing conversion of angiotensin I to angiotensin II—reducing vasoconstriction, aldosterone secretion, and cardiac remodeling; they also increase bradykinin (responsible for the dry cough side effect). ARBs (losartan, valsartan) block the AT1 receptor directly, providing similar RAAS blockade without affecting bradykinin metabolism (no cough). Calcium channel blockers (CCBs) have two subclasses: dihydropyridines (amlodipine, nifedipine) primarily cause arterial vasodilation by blocking L-type calcium channels in vascular smooth muscle, while non-dihydropyridines (diltiazem, verapamil) additionally reduce heart rate and AV conduction. Thiazide diuretics (hydrochlorothiazide, chlorthalidone) initially reduce blood volume through natriuresis, but their long-term antihypertensive effect is mediated by decreased peripheral vascular resistance through unclear mechanisms. Beta-blockers (metoprolol, atenolol) reduce cardiac output by decreasing heart rate and contractility; they are no longer first-line for uncomplicated hypertension but remain essential for specific compelling indications (HFrEF, post-MI, rate control). The 2017 ACC/AHA guidelines define hypertension as BP ≥130/80 mmHg and recommend first-line therapy with ACE inhibitors/ARBs, CCBs, or thiazide diuretics based on race, comorbidities,...