Mechanisms of Vasodilatation Induced by Nitrite Instillation in Intestinal Lumen: Possible Role of Hemoglobin

Abstract

It has been shown that nitrite can be reduced to nitric oxide (NO) in intestine and a number of other tissues and released into the blood to form nitrosylhemoglobin (NO-Hb), existing in an equilibrium with S-nitrosohemoglobin. The latter has been suggested to be an NO transporter to distant organs. The aim of this study was to define the pathway of nitrite reduction to form NO in intestinal wall and to estimate whether this pathway has an effect on peripheral circulation. We have shown that in rat intestine at pH 7.0 70% of nitrite is converted to NO in mitochondria. At pH 6.0, nonenzymatic nitrite reduction becomes as efficient as the mitochondrial pathway. To prove whether the NO formed from nitrite in intestine can induce vasodilatation, sodium nitrite was instilled into intestinal lumen and the concentration of NO formed and diffused into the blood was followed by measuring of NO-Hb complex formation. We found that the concentration of NO-Hb gradually increases with the increase of nitrite concentration in intestinal lumen. However, it was not always accompanied by a decrease in systemic blood pressure. Blood pressure dropped down only after NO-Hb reached a threshold concentration of approximately 10 microM. These data show that NO-Hb cannot provide enough NO for vasodilatation if the concentration of NO bound to Hb is< 10 microM. The exact mechanism underlying vasodilatation observed when the concentration of NO-bound Hb was > 10 microM is, however, not clear yet and requires further studies.

Blue Laser Light Increases Perfusion of a Skin Flap Via Release of Nitric Oxide from Hemoglobin

“…In the experiments with flap perfusion, we have shown that neither infusion of NO-Hb nor infusion of NO-Hb combined with laser irradiation decreases blood pressure or elevates cGMP levels in circulating blood (Figure 3). Stable blood pressure indicates that spontaneous NO liberation from nitrosyl-hemoglobin does not occur in vivo, which is in line with recently published data (21). In contrast to unaltered MAP and cGMP levels, the concentration of NO-Hb complexes in blood decreased in response to laser irradiation.…”

Nitrite as a vascular endocrine nitric oxide reservoir that contributes to hypoxic signaling, cytoprotection, and vasodilation

“…1) (10). Additional studies (43,55,92,93,97) have recently been published confirming the potent vasodilating effects of nitrite. Our group and others have now observed vasodilation at near physiological concentations (Ͻ5 M) in mice, rats, sheep, dogs, primates, and humans.…”

Nitrite Anion Provides Potent Cytoprotective and Antiapoptotic Effects as Adjunctive Therapy to Reperfusion for Acute Myocardial Infarction

“…3 The potent vasodilating effects of nitrite have been verified in a number of models. 12,14,19,20,39 The degree to which nitrite-induced vasodilation and coronary collaterals contribute to myocardial protection warrants consideration. It would require a very large sample size to determine the extent to which the statistically insignificant increase in microsphere blood flow (60-minute nitrite group) contributes to myocardial protection because the magnitude of effect is very small.…”