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
| Drugs | Mechanisms of Action | Common Indications |
|---|---|---|
Calcium channel blockers
|
Block voltage-gated L-type Ca2+ channels and thereby cause
|
|
β1-adrenoceptor antagonists
|
Block β1-adrenoceptors
|
|
α1-adrenoceptor antagonists
|
Block the binding of catecholamines to α1-adrenoceptors |
|
α2-adrenoceptor agonists
|
Selectively activate central α2-adrenoceptors and thereby inhibit sympathetic outflow from the CNS |
|
K+ channel openers
|
Open K+ channels in the plasma membrane of vascular smooth muscles thereby preventing the opening of C2+ channels causing arterial vasodilation |
|
Nitric oxide donors
|
Release NO, which activates guanylyl cyclase and increases dephosphorylation of myosin light chain in vascular smooth muscle causing vasodilation |
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