The potential of stimulating nitric oxide formation in the treatment of hypertension.
Hypertension is a leading cause of morbidity and mortality worldwide. A major pathophysiological factor contributing to hypertension is reduced nitric oxide (NO) bioavailability. Strategies to address this pathophysiological mechanism could offer significant advantages. Areas covered: In this review we aimed at examining a variety of drugs (statins, beta-adrenergic receptor blockers, calcium channel blockers, angiotensin converting enzyme inhibitors, angiotensin II type-1 receptor blockers) used to treat hypertension and other cardiovascular diseases, particularly with respect to their potential of increasing NO bioavailability and activity in the cardiovascular system. There is now evidence supporting the notion that many cardiovascular drugs activate NO signaling or enhance NO bioavailability as a contributing mechanism to their beneficial cardiovascular effects. Moreover, other drugs may attenuate NO inactivation by superoxide and other reactive oxygen species by exerting antioxidant effects. More recently, the NO oxidation products nitrite and nitrate have been acknowledged as sources of NO after recycling back to NO. Activation of the nitrate-nitrite-NO pathway is an alternate pathway that may generate NO from both anions and exert antihypertensive effects. Expert opinion: In this review, we provide an overview of the possible mechanisms by which these drugs enhance NO bioavailability and help in the therapy of hypertension.
a Department of Pharmacology, Ribeirao Preto Medical School , University of Sao Paulo , Ribeirao Preto , Brazil.
Lucas C
LC
Pinheiro
a Department of Pharmacology, Ribeirao Preto Medical School , University of Sao Paulo , Ribeirao Preto , Brazil.
Jose E
JE
Tanus-Santos
a Department of Pharmacology, Ribeirao Preto Medical School , University of Sao Paulo , Ribeirao Preto , Brazil.
Michele M
MM
Castro
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000959:Antihypertensive Agents; D000975:Antioxidants; D002317:Cardiovascular Agents; D017382:Reactive Oxygen Species; D009569:Nitric Oxide
Hypertension; nitrate; nitric oxide; nitric oxide synthase; nitrite