Vasodilators affect arteries and veins differently mainly due to:

1. More Muscle in Arteries: Arteries, especially arterioles (which control blood pressure), have significantly more smooth muscle in their walls compared to veins. Drugs that relax smooth muscle thus have a more pronounced effect on constricting or dilating arteries, impacting afterload (resistance the heart pumps against).
2. Veins as Volume Holders: Veins are "capacitance" vessels, meaning they hold a large blood volume and are more distensible with less muscle. Vasodilators that relax veins (like nitrates at low doses) primarily increase their capacity to hold blood, significantly reducing preload (the amount of blood returning to the heart).
3. Enzyme Differences: Some vasodilators, like nitroglycerin, are converted to their active form (nitric oxide) more efficiently by enzymes predominantly found in venous smooth muscle. This contributes to their initial preference for dilating veins.
   • mtALDH2 enzyme system is significantly more efficient at metabolizing organic nitrates like nitroglycerin in venous smooth muscle compared to arterial smooth muscle, particularly at lower, clinically relevant concentrations of the drug.

I. Mainly ARTERIOLAR Dilators (Reduce Afterload)

• Direct arteriolar vasodilators
  • Hydralazine:
    • Site: Arterioles
    • Mech: ↑cGMP → smooth muscle relaxation.
    • Uses: Severe HTN, HF (with nitrates, esp. in African Americans), HTN in pregnancy.
    • Side Effects: Drug-induced lupus, reflex tachycardia, fluid retention.
  • Minoxidil:
    • Site: Arterioles
    • Mech: Opens K+ channels → hyperpolarization → relaxation.
    • Uses: Refractory HTN, alopecia.
    • Side Effects: Hypertrichosis, reflex tachycardia, severe edema.
• Fenoldopam:
  • Site: Arterioles (esp. renal, coronary)
  • Mech: Dopamine D1 agonist.
  • Uses: Hypertensive emergency (esp. with renal insufficiency).
  • Side Effects: Hypotension, tachycardia, flushing.

II. Mainly VENOUS Dilators (Reduce Preload)

• Nitrates (Nitroglycerin, Isosorbide Dinitrate/Mononitrate):
  • Site: Veins >> Arteries (at higher doses, arteries also dilate)
  • Mech: ↑NO → ↑cGMP → relaxation.
  • Uses: Angina, ACS, acute HF.
  • Side Effects: Headache, flushing, hypotension, tolerance. (Contra: PDE-5 inhibitors, R. ventricular MI).

III. MIXED (Arteriolar & Venous) Dilators (Reduce Preload & Afterload)

• Sodium Nitroprusside:
  • Site: Arterioles = Veins
  • Mech: Direct NO release → ↑cGMP.
  • Uses: Hypertensive emergencies, severe acute HF.
  • Side Effects: Cyanide toxicity, severe hypotension.
• ACE Inhibitors (-prils):
  • Site: Arterioles > Venules (indirectly)
  • Mech: ↓Angiotensin II, ↑Bradykinin.
  • Uses: HTN, HFrEF, diabetic nephropathy.
  • Side Effects: Dry cough, angioedema, hyperkalemia, teratogenic. (Contra: Bilateral renal artery stenosis).
• ARBs (-sartans):
  • Site: Arterioles > Venules (indirectly)
  • Mech: Block AT1 receptors.
  • Uses: HTN, HFrEF (if ACEi intolerant).
  • Side Effects: Hyperkalemia, angioedema (less than ACEi), teratogenic. (Contra: Bilateral renal artery stenosis).
• Calcium Channel Blockers (CCBs):
  • Dihydropyridines (-dipines like Amlodipine, Nifedipine):
    • Site: Arterioles
    • Mech: Block L-type Ca²⁺ channels (vascular).
    • Uses: HTN, angina (incl. Prinzmetal).
    • Side Effects: Peripheral edema, flushing, reflex tachycardia, gingival hyperplasia.
  • Non-Dihydropyridines (Verapamil, Diltiazem):
    • Site: Heart & Arterioles
    • Mech: Block L-type Ca²⁺ channels (cardiac & vascular).
    • Uses: HTN, angina, rate control (AFib).
    • Side Effects: Bradycardia, AV block, constipation (verapamil). (Contra: HFrEF for these).