nitroarginine and Arterial-Occlusive-Diseases

We evaluated in the in situ vascularly isolated canine diaphragm the role of nitric oxide (NO) in the regulation of basal vascular resistance and vascular responses to increased muscle activity (active hyperemia), brief occlusions of the phrenic artery (reactive hyperemia), and changes in arterial pressure. The vasculature of the left hemidiaphragm was either pump-perfused at a fixed flow rate or autoperfused with arterial blood from the femoral artery. Endothelial nitric oxide synthase (NOS) activity was inhibited by intraphrenic infusion of L-arginine analogues such as N(G)-nitro-L-arginine, N(G)-nitro-L-arginine methyl ester and argininosuccinic acid. Active hyperemia was produced by low (2 Hz) frequency stimulation of the left phrenic nerve. Reactive hyperemia was measured in response to 10, 20, 30, 60, and 120 sec duration occlusions of the left phrenic artery and was quantified in terms of postocclusive blood flow, vascular resistance, hyperemic duration, and hyperemic volume. Infusion of NOS inhibitors into the vasculature of the resting diaphragm increased phrenic vascular resistance significantly and to a similar extent. Reactive hyperemic volume and reactive hyperemic duration were also significantly attenuated after NOS inhibition, however, peak reactive hyperemic dilation was not influenced by NOS inhibition. It was also found that enhanced NO release contribute by about 41% to active dilation elicited by continuous 2 Hz stimulation. In addition, NOS inhibition had no effect on O2 consumption of the resting diaphragm, but significantly attenuated the rise in diaphragmatic O2 consumption during during 2 Hz stimulation. The decline in diaphragmatic O2 consumption was due to reduction in blood flow. These results indicate that NO release plays a significant role in the regulation of diaphragmatic vascular tone and O2 consumption.

Topics: Animals; Argininosuccinic Acid; Arterial Occlusive Diseases; Arteries; Blood Vessels; Dogs; Electric Stimulation; Enzyme Inhibitors; Hyperemia; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Nitroarginine; Oxygen Consumption; Phrenic Nerve; Regional Blood Flow; Respiratory Muscles; Vascular Resistance; Vasodilation

Inhibition of an endothelium-derived relaxing factor (EDRF) may contribute to the pathogenesis of thrombotic arterial occlusions.. We measured the blood pressure and urinary excretion of protein, sodium, and potassium and histologically examined the brains, hearts, and kidneys in normotensive Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) fed on a diet containing: (a) EDRF inhibitor (L-N-nitroarginine:L-NNA); (b) L-arginine, which reverses the effect of L-NNA; or (c) both L-NNA and L-arginine for 1 to 8 weeks. In addition, we examined L-NNA-treated SHRSP, the blood pressures of which were lowered using hydralazine. Furthermore, we produced and examined Goldblatt's renal hypertensive rats, which are of a different type from those resulting from the L-NNA treatment.. Both WKY and SHRSP rats fed on a diet containing L-NNA suffered from hypertension and cerebral infarctions in a dose-dependent manner. Cerebral infarctions occurred whether or not SHRSP rats were treated with an antihypertensive agent when they were fed a high dosage of L-NNA. In contrast, SHRSP rats, treated simultaneously with both L-NNA and L-arginine, suffered few cerebral infarctions, although they were severely hypertensive. In addition, there were no cerebral infarctions in Goldblatt's renal hypertensive rats, although they suffered from advanced hypertension.. The data indicate that the inhibition of EDRF injures the vessel walls and encourages platelet adhesion to the damaged areas. The adhering platelets narrow the lumen with resultant thrombotic arterial occlusions. Pathophysiologic conditions that decrease EDRF synthesis appear to play an important role in cerebral, renal, and myocardial infarctions.

Topics: Animals; Arginine; Arterial Occlusive Diseases; Blood Pressure; Blood Vessels; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Hydralazine; Hypertension, Renovascular; Incidence; Microscopy, Electron; Nitric Oxide; Nitroarginine; Potassium; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sodium; Thrombosis; Time Factors; Vascular Diseases

To determine whether dilation of large coronary arteries normalizes shear during increased flow following brief occlusion, six dogs were instrumented to measure aortic and left ventricular pressures, left circumflex coronary artery external diameter, and coronary blood flow. The coronary artery was occluded for 15 or 30 s. Data were obtained before and after blockade of EDRF synthesis with nitro-L-arginine. Internal coronary artery diameter and wall shear were calculated on a moment-to-moment basis and the area under the flow curve was measured. Peak flow and shear rate were unaffected by NLA or by the occlusion duration. Flow curve area increased with the duration of occlusion. Internal and external diameters increased significantly for 15 s occlusions before NLA (by 4 +/- 1% in external diameter and by 11 +/- 4% in internal diameter) and for 30 s occlusions before NLA (by 5 +/- 1% in external diameter and by 14 +/- 5% in internal diameter) but not after NLA. Adenosine infusions of 0.05, 0.10, 0.50, and 1.0 mumol/kg/min were also used to dilate the coronary arteries. With each infusion, flow, shear and diameter were allowed to reach steady state. Steady state shear was reduced only slightly and did not approach the baseline state. We conclude that increased shear rate causes an increase in coronary artery diameter which is EDRF dependent. Increased coronary artery diameter during reactive hyperemia and adenosine infusions did not normalize wall shear.

Topics: Adenosine; Animals; Arginine; Arterial Occlusive Diseases; Coronary Vessels; Dogs; Infusions, Intra-Arterial; Nitric Oxide; Nitroarginine; Stress, Mechanical; Vasodilation

Nitric oxide has been implicated as a mediator of glutamate excitotoxicity in primary neuronal cultures.. A number of indicators of brain nitric oxide production (nitric and cyclic guanosine monophosphate [cGMP] concentrations and nitric oxide synthase activity) were examined after bilateral carotid ligation and right middle cerebral artery occlusion in adult rats.. Brain nitrite was significantly increased in the right versus left cortex 5, 10, and 20 minutes after middle cerebral artery occlusion (P < .05), with a return to baseline at 60 minutes. There were no significant changes in cerebellar concentrations. Cortical levels of cGMP were increased at 10, 20, and 60 minutes after occlusion, with significant right-to-left differences (P < .05). Cerebellar concentrations of cGMP were also increased but without significant side-to-side differences. Nitric oxide synthase activity increased approximately 10-fold from baseline 10 minutes after occlusion in the right cortex but decreased markedly by 60 minutes from its peak at 10 minutes. The right-to-left difference in nitric oxide synthase activity was significant at 20 minutes (P < .05). Pretreatment of rats with NG-nitro-L-arginine, a nitric oxide synthase inhibitor, abolished the rise in nitrite and cGMP.. These results suggest that a sharp transient increase in the activity of nitric oxide synthase occurs during the first hour of cerebral ischemia, which leads to a burst in nitric oxide production and activation of guanylate cyclase.

Topics: Amino Acid Oxidoreductases; Analysis of Variance; Animals; Arginine; Arterial Occlusive Diseases; Brain; Cerebellum; Cerebral Arterial Diseases; Cerebral Cortex; Cyclic GMP; Functional Laterality; Ischemic Attack, Transient; Male; Nitric Oxide; Nitric Oxide Synthase; Nitrites; Nitroarginine; Rats; Rats, Wistar