Snapshot A 29-year-old G2P1 woman presents to her obstetrician at 18 weeks gestation for a check-up. Aside from mild nausea earlier in her pregnancy, she feels well overall and has no major complaints. At her last checkup 3 weeks ago, her blood pressure was 150/86 mmHg. Today, her blood pressure is 152/88 mmHg. She is started on oral hydralazine for confirmed chronic hypertension. Introduction Direct-acting vasodilators function by dilating arterial vessels without any direct activity on venous circulation Drugs hydralazine oral or parenteral agent used to treat hypertensive diseases minoxidil topical agent used to treat male pattern baldness Hydralazine Mechanism of action the exact mechanism is unclear appears to act via multiple simultaneous mechanisms stimulates nitric oxide release from vascular endothelium → ↑ cGMP → smooth muscle relaxation opens K+ channels → hyperpolarizes vascular smooth muscle → smooth muscle relaxation blocks IP3-dependent release of calcium from the smooth muscle sarcoplasmic reticulum → decreased calcium availability → impaired smooth muscle contraction Physiologic effects decreases peripheral resistance activates baroreflex-mediated vasoconstriction increases venous return to the heart increases catecholamine-mediated inotropy and chronotropy often co-administered with a sympathetic inhibitor (e.g., β-blocker) to inhibit this compensatory response Clinical use hypertensive crisis congestive heart failure ↓ afterload → ↑ stroke volume and ↑ ejection fraction hypertensive diseases of pregnancy chronic hypertension gestational hypertension moderate to severe hypertension not first-line due to short half-life and precipitation of reflex sympathetic activation Toxicity contraindicated in patients with coronary artery disease can ↑ cardiac demand due to baroreflex-mediated sympathetic activation fluid retention headache lupus-like syndrome (especially for slow acetylators) Minoxidil Mechanism of action opens K+ channels → hyperpolarizes vascular smooth muscle → smooth muscle relaxation Clinical use male pattern baldness (androgenic alopecia) Toxicity hypertrichosis