Snapshot A 31-year-old G1P0 woman presents to her obstetrician at 19 weeks gestation for a check-up. She feels well and has no complaints other than some minor back pain. At her last check-up 3 weeks ago, her blood pressure was 152/88 mmHg. Today, her blood pressure is 156/90 mmHg. She is diagnosed with chronic hypertension and started on oral hydralazine. 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 coadministered 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