The upper limit of cerebral autoregulation was studied in pre- or early established hypertension in spontaneously hypertensive rats (SHR). Cerebral blood flow (CBF) was measured with the hydrogen clearance method, and wall/lumen ratio of cerebral arteries was morphometrically measured with the freeze-substitution technique. To test autoregulation, phenylephrine was intravenously infused to cause stepwise increments of blood pressure. Unilateral superior cervical ganglionectomy was carried out to examine the effects of sympathetic denervation on CBF autoregulation and thickness of vascular wall. Resting blood pressure at 4 weeks, 3 months and 6 months of age were 89 +/- 3 mm Hg (mean +/- SEM), 140 +/- 6 and 165 +/- 6, respectively. Baseline CBF was slightly diminished with age; 50.6 +/- 9.2 ml/100 g/min at 4 weeks, 49.8 +/- 8.1 at 3 months and 44.1 +/- 5.6 at 6 months. The upper limit of autoregulation was markedly raised with age; 118 +/- 5 mm Hg at 4 weeks, 180 +/- 7 at 3 months and 208 +/- 10 at 6 months. Acute sympathetic denervation lowered the upper limits to 105 +/- 2, 162 +/- 4 and 185 +/- 7 mm Hg, respectively. On the other hand, in chronic denervation which was made at 4 weeks of age, the upper limit of autoregulation in the denervated hemisphere was slightly lower than that in innervated hemisphere at 2 months (165 +/- 5 and 178 +/- 6 mm Hg), and at 5 months (202 +/- 8 and 215 +/- 8 mm Hg) after ganglionectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

PubMedDate not supplied

Cerebral blood flow and tissue metabolism in experimental cerebral ischemia of spontaneously hypertensive rats with hyper-, normo-, and hypoglycemia.

The present study was designed to clarify the effect of blood glucose level on cerebral blood flow and metabolism during and after acute cerebral ischemia induced by bilateral carotid ligation (BCL) in spontaneously hypertensive rats (SHR). Blood glucose levels were varied by intraperitoneal infusion of 50% of glucose (hyperglycemia), insulin with hypertonic saline (hypoglycemia) or hypertonic saline (normoglycemia). Cerebral blood flow (CBF) in the parietal cortex and thalamus was measured by hydrogen clearance technique, and the supratentorial metabolites of the brain frozen in situ were determined by the enzymatic method. In non-ischemic animals, blood glucose levels had no influence on the supratentorial lactate, pyruvate or adenosine triphosphate (ATP) concentrations. In ischemic animals, however, cortical CBF was reduced to less than 1% of the resting value at 3 hours after BCL. However, there were no substantial differences of CBF during and after ischemia among 3 glycemic groups. Cerebral lactate in the ischemic brain greatly increased in hyperglycemia (34.97 +/- 1.29 mmol/kg), moderately in normoglycemia (23.43 +/- 3.13 mmol/kg) and less in hypoglycemia (7.20 +/- 1.54 mmol/kg). In contrast, cerebral ATP decreased in hyperglycemia (0.93 +/- 0.19 mmol/kg) as much as it did in normoglycemia (1.04 +/- 0.25 mmol/kg), while ATP reduction was much greater in hypoglycemia (0.45 +/- 0.05 mmol/kg). At 1-hour recirculation after 3-hour ischemia, ATP tended to increase in all groups of animals, indicating the recovery of energy metabolism. Such metabolic recovery after recirculation was good in hypo- and normoglycemia, and was also evident in hyperglycemia. Our results suggest that hyperglycemia is not necessarily an unfavorable condition in acute incomplete cerebral ischemia.

Adenosine Triphosphate↗

PubMedDate not supplied

Immunohistochemical localization of microcystin-LR in the liver of mice: a study on the pathogenesis of microcystin-LR-induced hepatotoxicity.

The relationship between the intralobular sites of hepatotoxic injury and the distribution of microcystin-LR (MCLR), an inhibitor of protein phosphatases 1 (PP1) and 2A (PP2A), was examined using an immunohistochemical method with a monoclonal antibody specific to MCLR on the livers of mice receiving a single i.p. injection of the MCLR. Immunoblotting and high-performance liquid chromatography analyses of liver extracts were also performed to determine the binding form of MCLR to PP1 and PP2A (MCLR-PP1/PP2A adducts) and free MCLR. Immunohistochemistry revealed a discernible intensity of staining in the centrilobular regions where hemorrhage and apoptosis occurred. In these regions, immunopositivity was evident in the cytoplasm and nuclei of the hepatocytes; some apoptotic cells were also immunopositive. In contrast, coagulative necrosis, which was mainly evident in the midlobular regions, was completely negative. Analysis of liver extracts demonstrated MCLR-PP1/PP2A adducts, but free MCLR was below detection limit. These results suggest that the immunohistochemical localization of MCLR in centrilobular hepatocytes is closely associated with the onset of hemorrhage and apoptosis and is related to adduct formation. The occurrence of coagulative necrosis however might also be related to other factors such as ischemia/hypoxia.

Animals↗

PubMedDate not supplied

Electron microscopic studies on ATPase activities in myocardial infarction.

Comparative studies of the fine structural changes and histochemical examination of adenosine triphosphatase (ATPase) activity were performed in canine ischemic heart muscle cells following left coronary artery ligation. In the intact myocardial cells, the ATPase activities were observed most intensely in the sarcoplasmic reticulum (SR), particularly in the terminal cisternae (TC), and moderately around gap junctions of the intercalated discs and on myofilaments. Ischemic cellular changes occurred three to 24 hours after coronary ligation and became severe after three to seven days. ATPase activities decreased at around 48 hours and also became weak at three to seven days. Two to three weeks after ligation, improvement of the fine structure and increase in ATPase activities were observed in the ischemic cells, suggesting recovery. ATPase activities in the ischemic cardiac cells appeared to be decreased in parallel with the process of the fine structural changes.

Adenosine Triphosphatases↗

PubMedDate not supplied

Cerebral autoregulation in young spontaneously hypertensive rats. Effect of sympathetic denervation.

Autoregulation of cerebral blood flow was studied with the hydrogen clearance method during development of hypertension in young spontaneously hypertensive rats. To examine the influence of sympathetic nerves on autoregulatory range, the unilateral superior cervical ganglion was removed 2 hours or 2 or 5 weeks before the study. Wall-to-lumen ratio of cerebral arteries was determined with freeze substitution technique. Basal blood pressures were 87 +/- 1 mm Hg (mean +/- SEM) at 4 weeks of age, 105 +/- 2 at 6 weeks, and 126 +/- 3 at 9 weeks, although resting cerebral blood flow was unchanged. Initially, cerebral blood flow remained relatively constant when the blood pressure was raised by intravenous infusion of phenylephrine. The upper limits of cerebral blood flow autoregulation in these groups were 110 +/- 4 mm Hg, 126 +/- 7, and 159 +/- 6 respectively. Acute ganglionectomy significantly lowered the upper limits (p less than 0.05), but chronic denervation did not affect the autoregulatory range. The wall-to-lumen ratios of cerebral arteries were 0.136 +/- 0.007 at 4 weeks and 0.130 +/- 0.005 at 9 weeks. These differences were not significant, nor did sympathetic denervation alter the ratio. These results indicate that (1) the upward shift of the autoregulation is closely related to a rise in the basal blood pressure, (2) acute interruption of sympathetic nerves modulates the autoregulatory range, and (3) adaptation of cerebral blood flow autoregulation to early developmental hypertension may be attributed to factors other than vascular smooth muscle hypertrophy.

Animals↗