Nitric oxide, angiotensin II, and hypertension.
Although initially adaptive, the changes that accompany hypertension, namely, cell growth, endothelial dysfunction, and extracellular matrix deposition, eventually can become maladaptive and lead to end-organ disease such as heart failure, coronary artery disease, and renal failure. A functional imbalance between angiotensin II (Ang II) and nitric oxide (NO) plays an important pathogenetic role in hypertensive end-organ injury. NO, an endogenous vasodilator, inhibitor of vascular smooth muscle and mesangial cell growth, and natriuretic agent, is synthesized in the endothelium by a constitutive NO synthase. NO antagonizes the effects of Ang II on vascular tone, cell growth, and renal sodium excretion, and also down-regulates the synthesis of angiotensin-converting enzyme (ACE) and Ang II type 1 receptors. On the other hand, Ang II decreases NO bioavailability by promoting oxidative stress. A better understanding of the pathophysiologic mechanisms involved in hypertensive end-organ damage may aid in identifying markers of cardiovascular susceptibility to injury and in developing therapeutic interventions. We propose that those antihypertensive agents that lower blood pressure and concomitantly restore the homeostatic balance of vasoactive agents such as Ang II and NO within the vessel wall would be more effective in preventing or arresting end-organ disease.
Zhou
Ming-Sheng
MS
Nephrology-Hypertension Division, Vascular Biology Institute, University of Miami School of Medicine, Veterans Affairs Medical Center, FL 33125, USA.
Schulman
Ivonne H
IH
Raij
Leopoldo
L
D000804:Angiotensin II / Q000187:drug effects / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000517:prevention & control; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism*; D011379:Prognosis; D012079:Renal Circulation / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology; D012307:Risk Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D009569:Nitric Oxide