nitroarginine and Stroke

We studied the effect of sodium nitrite in doses of 5 and 50 mg/kg and NO synthase inhibitor L-NNA in a dose of 20 mg/kg on the course of experimental ischemic stroke caused by occlusion of both carotid arteries. Sodium nitrite and NO synthase inhibitor were administered 1 h prior to occlusion of еру carotid arteries and 5 sec after brain ischemia. Sodium nitrite in a dose of 5 mg/kg had a protective effect on the time course of neurological disorders and reduced animal mortality. NO synthase inhibitor L-NNA aggravated the neurological symptoms.

Topics: Animals; Carotid Arteries; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Male; Nitric Oxide Synthase; Nitroarginine; Rats; Rats, Wistar; Sodium Nitrite; Statistics, Nonparametric; Stroke; Treatment Outcome

We investigated the effect of ischemia and reperfusion on the vasoactive function of penetrating brain parenchymal arterioles under pressurized conditions.. Parenchymal arterioles (< 50 microm in diameter) from within the middle cerebral artery territory were dissected from male Wistar rats that were either nonischemic control (n = 16) or ischemic for one hour and reperfused for 24 hours (n = 16) by temporary filament occlusion of the middle cerebral artery. Arterioles were mounted on glass cannulas within an arteriograph chamber that allowed for the measurement of lumen diameter and control over intravascular pressure.. After one hour of equilibration at 10 mmHg, spontaneous myogenic tone developed in both groups of animals, constricting control arterioles from 69 +/- 9 to 49 +/- 11 microm (29.5 +/- 10.2%) and ischemic arterioles from 66 +/- 9 to 45 +/- 11 microm (33.1 +/- 14.1%); p > 0.05. Contraction to the nitric oxide synthase inhibitor nitro-L-arginine (10(-4)M) was significantly diminished in ischemic arterioles, constricting only 3.2 +/- 3.3 vs. 15.6 +/- 12.5% in control arterioles (p = 0.017). Both groups dilated to nifedipine; however, the response was significantly diminished after ischemia. The EC50 for nifedipine in control arterioles was 3.54 +/- 0.11 vs. 9.90 +/- 0.71 nM for ischemic arterioles (p = 0.024).. These findings demonstrate that functional changes occur in brain parenchymal arterioles after ischemia and reperfusion, a result that may significantly influence stroke outcome by altering blood flow to an ischemic region.

Topics: Animals; Arterioles; Brain; Brain Ischemia; Cerebrovascular Circulation; Enzyme Inhibitors; Male; Middle Cerebral Artery; Nifedipine; Nitric Oxide Synthase; Nitroarginine; Rats; Rats, Wistar; Reperfusion Injury; Stroke; Vasoconstriction; Vasodilator Agents

To evaluate whether the elevated blood pressure induced by chronic treatment with N(omega)-nitro-L-arginine methyl ester (L-NAME) contributes to an impairment of endothelium-dependent relaxation (EDR), the effects of chronic treatment of Wistar rats with L-NAME on systolic blood pressure, pulmonary arterial blood pressure and EDR of the pulmonary arteries were studied and compared with those of stroke-prone spontaneously hypertensive rats (SHRSP). While the systolic blood pressure (SBP) of Wistar rats was increased above that of controls by chronic treatment with L-NAME, it was still significantly lower than that of SHRSP. Chronic treatment with L-NAME did not affect pulmonary arterial blood pressure. On the other hand, the pulmonary arterial blood pressure of SHRSP was slightly but significantly higher than that of the control normotensive Wistar Kyoto rats (WKY). EDR in response to acetylcholine in the pulmonary artery of L-NAME-treated rats was significantly smaller than that in control Wistar rats. The EDR markedly increased in the presence of L-arginine and completely disappeared in the presence of N(omega)-nitro-L-arginine. Indomethacin hardly affected EDR. In preparations from SHRSP, the EDR was not different from that in those from WKY. Relaxation induced by sodium nitroprusside was identical in all preparations. Elevation of SBP and the impairment of EDR observed in L-NAME-treated rats recovered two weeks following cessation of treatment. These results suggest that the impaired EDR in the pulmonary artery of L-NAME-treated rats is not due to an L-NAME-induced increase in blood pressure but due to the inhibition of nitric oxide synthase by the drug remaining in the endothelium.

Topics: Animals; Arginine; Blood Pressure; Body Weight; Cardiovascular Agents; Endothelium, Vascular; Enzyme Inhibitors; Genetic Predisposition to Disease; Hypertension; Indomethacin; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Donors; Nitroarginine; Nitroprusside; Pulmonary Artery; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Wistar; Stroke; Vasodilation

Difference in effects of stretch tension on endothelium-derived nitric oxide (EDNO)-dependent depression of noradrenaline (NA)- and high-K+-induced contraction between the aortae from normotensive Wistar Kyoto rats (WKY) a nd stroke-pronespontaneously hypertensive rats (SHRSP) was studied. NA-induced contraction in preparations both from WKY and SHRSP was augmented in the presence of N(omega)-nitro-L-arginine (L-NNA). This augmentation was minimized when the spontaneous tone, which was more prominent in preparations from SHRSP, was subtracted and the effects of L-NNA became less prominent in preparations from SHRSP. The effects of L-NNA were maximal at the stretch tension of 15 mN and, then, decreased as stretch tension increased in both preparations when the spontaneous tone was subtracted. The effects of L-NNA were less prominent when the contraction was initiated by high-K+, although the effects of stretch on high-K+-induced contraction were similar to that of NA-induced contraction. These results suggested 1) that both NA- and high-K+-induced contractions are depressed by EDNO, 2) that the release of EDNO induced by high-K+ is less than that by NA, 3) that increase in stretch tension decreases the release of EDNO, and 4) that the depressive effect of EDNO on contraction is impaired in the aorta of SHRSP.

Topics: Animals; Aorta; Blood Pressure; Dose-Response Relationship, Drug; Endothelium, Vascular; Enzyme Inhibitors; Genetic Predisposition to Disease; Nitric Oxide; Nitroarginine; Norepinephrine; Potassium; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reference Values; Stress, Mechanical; Stroke; Vasoconstriction

To determine the effects of chronic nitric oxide (NO) blockade on the pulmonary vasculature, 58-day-old spontaneously hypertensive rats of the stroke-prone substrain (SHRSP) and Wistar-Kyoto rats (WKY) received N(omega)-nitro-L-arginine (L-NNA; 15 mg. kg(-1). day(-1) orally for 8 days). Relaxation to acetylcholine (ACh) in hilar pulmonary arteries (PAs), the ratio of right ventricular (RV) to body weight (RV/BW) to assess RV hypertrophy (RVH), and the percent medial wall thickness (WT) of resistance PAs were examined. L-NNA did not alter the PA relaxation, RV/BW, or WT in WKY. Although the PA relaxation and RV/BW in control SHRSP were comparable to those in WKY, the WT was increased (31 +/- 2 vs. 19 +/- 1%). L-NNA-treated SHRSP showed two patterns: in one group, the relaxation, RV/BW, and WT were comparable to those in the control SHRSP; in the other, impaired relaxation (36 +/- 7 vs. 88 +/- 4% for WKY) was associated with an increase in WT (37 +/- 1%) and RV/BW (0. 76 +/- 0.05). Thus the abnormal pulmonary vasculature in SHRSP at <10 wk of age is not accompanied by impaired relaxation in PAs or RVH; however, impaired relaxation is associated with increased WT and RVH.

Topics: Animals; Blood Pressure; Blood Vessels; Cyclic AMP; Cyclic GMP; Endothelium, Vascular; Enzyme Inhibitors; Genetic Predisposition to Disease; Hypertension, Pulmonary; Hypertrophy, Left Ventricular; Hypertrophy, Right Ventricular; Lung; Nitric Oxide Synthase; Nitroarginine; Pulmonary Circulation; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Stroke; Vasodilation