Cardiovascular regulation by endogenous nitric oxide is essential for survival after acute haemorrhage

Abstract

Our previous studies have indicated that endogenous nitric oxide serves as a physiologically important inhibitor of vascular tone during acute haemorrhage. This vasodilator action attenuates the concomitant reflex adrenergic constriction and thereby prevents critical reduction of tissue blood flow. The present study aimed to evaluate the overall importance of this nitric oxide regulation for survival after acute haemorrhage. This was done by comparative observations of survival time and circulatory, metabolic and histopathological changes after an acute standardized lethal blood loss (45%) in cats exposed to nitric oxide synthase (NOS) inhibition and in matched control animals with intact nitric oxide regulation. NOS inhibition was instituted by intravenously administered N omega-nitro-L-arginine methyl ester. The survival time averaged 2 h 49 min in the NOS-blocked animals and 10 h 14 min in the control animals (P< 0.001). NOS inhibition thus reduced the posthaemorrhagic survival time to < 30% of that in the control cats. Haemorrhage in the NOS-blocked animals led to rapidly developing arterial hypotension, increased anaerobic metabolism, metabolic lactacidosis, hyperkalaemia, and morphological tissue damage especially in heart and liver, in spite of maintained arterial normoxia, which signifies tissue hypoxia caused by seriously impaired nutritional blood supply. At the time of death of the NOS-blocked cats, the control animals still exhibited a virtually normal circulatory/metabolic state. A much later, and more slowly developing circulatory/metabolic deterioration was observed in the control animals. These differences between the two groups of animals indicate that nitric oxide release, by its vasodilator action, to a significant extent helps to maintain an adequate nutritional blood supply to the tissues in acute haemorrhage.

Acute and long‐term effects of modified hemoglobin (HBOC‐201) in a rat model of hypertension and chronic kidney disease

“…In addition, NO scavenging effects have been widely reported and this is the focus of the present discussion, given the evidence that a state of NO deficiency already occurs in CKD (see below). A number of workers have reported that l ‐arginine supplementation (which boosts endogenous NO production) is a helpful adjunct during resuscitation from hemorrhage 20,21 and that concomitant NOS inhibition reduces survival 22 . Alternatively, raising the BP may be helpful in maintaining organ perfusion, at least when hypotension is present (as in hemorrhage).…”

Effects of Acute Nitric Oxide Synthase Inhibition on Lower Leg Vascular Function in Chronic Tetraplegia

“…The administration of 1 mg?kg 21 body weight L-NAME in people with tetraplegia increased systemic blood pressure and lower leg vascular resistance to control group levels. Baroreceptor-dependent vasoregulation is an important mechanism for mitigating the potentially deleterious consequences of hypertensive episodes to the arterial endothelium (27)(28)(29). In the control group, buffering of the blood pressure response to NOS inhibition via the arterial baroreceptors and synergistic humoral pathways was present to modulate changes to vascular tone and, thus, vascular resistance (30,31); the observed arterial vasoconstrictor responses to NOS inhibition were the result of the sum of intact vasoregulatory pathways responding to the pressor effect of NOS inhibition.…”

“…In neurologically intact humans, rapid activation of endothelial-derived NOS and production of NO in response to abrupt and dynamic fluctuations of blood flow are essential to enable adequate perfusion of metabolically active organs/tissue during exercise or stressful situations (27,28), as well as for hyperemic dilatation (43) and the protection against pressuremediated injury to vital organs and tissues (29). The release of NO facilitates vasodilatation (43) and buffers the elevated arterial vascular resistance through a reduction of sympathetic nerve activity to the vascular smooth muscle (29).…”

Nitrosation of Uric Acid by Peroxynitrite

“…It is possible that a mimic of the nitrated uric acid product could be utilized to alleviate myocardial ischemic syndromes following ischemia/ reperfusion, cardioplegic ischemic arrest, coronary artery thrombosis after thrombolysis, and restenosis after transluminal coronary angioplasty (63,64). The uric acid nitrosation product may play a pivotal role in human pathophysiology by releasing ⅐NO, which could decrease vascular tone and increase tissue blood flow (65,66). The nitrated uric acid product may also exhibit anti-inflammatory properties by inhibiting platelet aggregation/adherence (67) as well as by attenuating leukocyte adhesion to the endothelial cell surface (68).…”