Drugs that Regulate Vascular Tone

Vascular tone is another key determinant of tissue perfusion. Vascular smooth muscle cells are the functional regulatory units that integrate a variety of signals initiated by (1) local factors (e.g., H+, CO2, stretch), (2) endothelium-derived signaling molecules (e.g., nitric oxide, prostacyclin), (3) neurotransmitters (e.g., epinephrine), and (4) hormones (e.g., vasopressin) to optimize vascular tone.5 Ultimately, vascular smooth muscle tone is determined by the intracellular Ca2+ ion concentration.

Drugs in the top 300 that regulate vascular tone (Tables 2 and 3) include (1) Ca2+ channel blockers, (2) β1-adrenoceptor antagonists, (3) α1-adrenoceptor antagonists, (4) α2-adrenoceptor agonists, (5) K+ channel openers, (6) nitric oxide donors, and (7) inhibitors of the RAAS.2,5,6,10 These drug categories are intended for the management of systemic and pulmonary hypertension, ischemic heart disease (i.e., chronic coronary artery disease and acute coronary syndromes), and congestive heart failure.5,6

Table 3. Drugs that Regulate Vascular Tone.2,5,6,10
Drugs Mechanisms of Action Common Indications
Calcium channel blockers
  • Amlopidine
  • Amlopidine w/ benazepril
  • Amlopidine w/ olmesartan
  • Diltiazem
  • Nifedipine
  • Verapamil
Block voltage-gated L-type Ca2+ channels and thereby cause
  • Vasodilation
  • Depressed cardiac contractility
  • Depressed SA-node automaticity
  • Depressed AV-node conduction velocity
  • Hypertension
  • Stable angina pectoris
  • Exertional angina pectoris
  • Unstable angina pectoris
  • Coronary spasm
  • Atrial flutter
  • Atrial fibrillation
β1-adrenoceptor antagonists
  • Metoprolol
  • Atenolol
  • Atenolol w/chlorthalidone
  • Carvedilol
  • Propranolol
  • Nebivolol
  • Labetalol
  • Nadolol
  • Bisoprolol
  • Bisoprolol w/hydrochlorothiazide
Block β1-adrenoceptors
  • Propranolol and nadolol also block β2-adrenoceptors
  • Labetalol and carvedilol also block β2- and α1- adrenoceptors
  • Hypertension
  • Angina pectoris
  • Post-MI syndrome
  • Heart failure
  • Cardiac arrhythmia
α1-adrenoceptor antagonists
  • Doxazosin
  • Terazosin
  • Prazosin
Block the binding of catecholamines to α1-adrenoceptors
  • Hypertension
α2-adrenoceptor agonists
  • Clonidine
  • Guanfacine
Selectively activate central α2-adrenoceptors and thereby inhibit sympathetic outflow from the CNS
  • Hypertension
K+ channel openers
  • Hydralazine
Open K+ channels in the plasma membrane of vascular smooth muscles thereby preventing the opening of C2+ channels causing arterial vasodilation
  • Moderate to severe hypertension
Nitric oxide donors
  • Nitroglycerin
  • Isosorbide mononitrate
  • Ranolazine
Release NO, which activates guanylyl cyclase and increases dephosphorylation of myosin light chain in vascular smooth muscle causing vasodilation
  • Acute angina pectoris (nitroglycerin)
  • Prophylaxis for ischemic heart disease