Hydralazine combined with isosorbide dinitrate is an alternative to ACE inhibitors in heart failure patients with renal failure. Hydralazine's mechanism of reducing cardiac afterload is:

• A Inhibition of phosphodiesterase-3 reducing intracellular calcium in vascular smooth muscle
• B Alpha-1 adrenoceptor blockade reducing sympathetic vasoconstrictor tone
• C Nitric oxide donation directly vasodilating arterioles
• D Direct arteriolar smooth muscle relaxation by opening ATP-sensitive potassium channels ✓

Explanation

Hydralazine directly relaxes arteriolar smooth muscle by opening ATP-sensitive potassium channels (KATP channels), causing membrane hyperpolarization that reduces calcium influx through voltage-gated L-type calcium channels. This selective arteriolar dilation reduces systemic vascular resistance (afterload) without significant venodilatory effect. Isosorbide dinitrate provides complementary venodilation (preload reduction) through nitric oxide release.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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