Nitrate and nitrite-based therapy to attenuate cardiovascular remodelling in arterial hypertension

Basic Clin Pharmacol Toxicol. 2021 Jan;128(1):9-17. doi: 10.1111/bcpt.13474. Epub 2020 Aug 28.


Hypertension is a highly prevalent disease marked by vascular and cardiac maladaptive remodelling induced mainly by renin-angiotensin system activation followed by oxidative stress. Here, we briefly describe these damages and review the current evidence supporting a potential role for nitrate and nitrite as antihypertensive molecules that act via nitric oxide (NO) formation-dependent and NO formation-independent mechanisms and how nitrate/nitrite inhibits cardiovascular remodelling in hypertension. The renin-angiotensin system activation and oxidative stress converge to activate proteases involved in cardiovascular remodelling in hypertension. Besides these proteases, several investigations have demonstrated that reduced endogenous NO bioavailability is a central pathological event in hypertension. In this regard, nitrate/nitrite, long considered inert products of NO, is now known as physiological molecules able to reduce blood pressure in hypertensive patients and in different experimental models of hypertension. These effects are associated with the formation of NO and other NO-related molecules, which could induce S-nitrosylation of target proteins. However, it remains unclear whether S-nitrosylation is an essential mechanism for the anti-remodelling effects of nitrate/nitrite in hypertension. Moreover, nitrate/nitrite produces antioxidant effects associated with the inhibition of signalling pathways involved in cardiovascular remodelling. Together, these findings may help to establish nitrate and nitrite as effective therapies in hypertension-induced cardiovascular remodelling.

Keywords: heart; metalloproteinases; nitrate; nitrite; vessels.

Publication types

  • Review

MeSH terms

  • Animals
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Arteries / drug effects
  • Arteries / metabolism
  • Arteries / physiopathology
  • Heart / drug effects
  • Heart / physiopathology
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / metabolism
  • Hypertension / physiopathology
  • Hypertrophy, Left Ventricular / drug therapy*
  • Hypertrophy, Left Ventricular / metabolism
  • Hypertrophy, Left Ventricular / physiopathology
  • Myocardium / metabolism
  • Nitrates / adverse effects
  • Nitrates / therapeutic use*
  • Nitric Oxide / metabolism
  • Nitrites / adverse effects
  • Nitrites / therapeutic use*
  • Oxidative Stress / drug effects
  • Renin-Angiotensin System / drug effects
  • Vascular Remodeling / drug effects*
  • Ventricular Function, Left / drug effects*
  • Ventricular Remodeling / drug effects*


  • Antihypertensive Agents
  • Nitrates
  • Nitrites
  • Nitric Oxide