Renal response to acute saline loading in Sabra hypertension-prone and-resistant rats

Summary The renal handling of an oral isotonic saline load was studied in hypertension-prone (SBH), hypertension-resistant (SBN) and the parental Sabra (SB) rats. The diuretic and natriuretic response of SBH rats was unequivocally diminished, thus lending further support to the concept of impaired salt handling in hypertension.This work was supported in part by a grant from Bayer AG, FRG.     

A transbasisphenoidal approach for selective occlusion of the middle cerebral artery in rats

Summary The authors report a new model of focal cerebral ischemia following a selective occlusion of the middle cerebral artery in rats, without additional insults of hypoxia, hypotension and handling of carotid and vertebral arteries, as required in previously described models.     

Defective phosphoinositide metabolism in primary hypertension

An increase in free cytosolic calcium content has been reported in essential hypertension. Since within the membrane, the phosphoinositides participate in the control of cell calcium homeostasis, we investigated whether impaired phosphoinositide metabolism could account for the calcium handling abnormality observed in hypertensives. In erythrocyte membranes of hypertensives the activity of kinases involved in polyphosphoinositide formation appears to be impaired and could be related to the alteration in calcium handling binding capacity and ATP-dependent calcium transport. In platelets of hypertensives, the hyperactivity of phospholipase C (observed even in the absence of calcium in the external medium) is likely to be responsible for the hypersensitivity of cells to various agonists. These observations are consistent with the hypothesis that in cells from hypertensives, a membrane defect linked to phosphoinositide metabolism is involved in the overall calcium handling defect.     

Experimental liver fibrosis induced in rats receiving high doses of alcohol and alternating between regular and vitamin-depleted diets

Liver fibrosis was induced in rats by simulating human alcoholic eating and drinking patterns. Alcohol addiction was established by gradually increasing the ethanol concentration in the drinking water; salts were added at the terminal stage. The hepatocytes of rats receiving alcohol concentrations exceeding 50% (v/v) (similar to vodka) exhibited alcoholic hyaline (Mallory bodies). Alcoholic liver fibrosis was induced by alternating between regular and autoclaved (vitamin-depleted) diets, simulating the irregular eating habits of human alcoholics. In the livers of rats receiving 70% (v/v) ethanol (comparable to absinthe) with 25% saline and fed the alternating diets, pericellular fibrosis was induced. No significant difference in calorie intake between control and alcohol rats was detected except when rats underwent drinking bouts (heavy drinking phase). This indicates that neither a high-fat diet nor a choline-depleted diet is necessary to induce the alcoholic fibrosis seen in human alcoholics.     

Enhanced reactivity towards flunarizine in cerebrovascular bed of spontaneously hypertensive rats

Cerebral blood flow (CBF) was measured and cerebrovascular resistance (CVR) was calculated in anesthetized spontaneously hypertensive rats (SHR) and normotensive rats (NR) following the administration of incremental dosages of i.v. flunarizine or papaverine. CBF and CVR changes following papaverine were the same in both groups of rats irrespective of the dose of the drug. The effect of flunarizine was much more pronounced in SHR than in NR. The results point out the greater dependency of basal cerebrovascular tone in SHR upon Ca2+ influx into vascular smooth muscle cells.     

Changes with hypertension and maturation in the response of stomach fundus to acetylcholine

Summary The purpose of these experiments was to compare the contractile response to ACh of stomach fundal strips from hypertensive (SHR) and normotensive (WKY) rats during the development of hypertension. The results indicate that the reactivity to ACh is the same in fundal strips from young SHR and WKY rats; however, with maturation strips from WKY rats undergo a reduction in responsiveness which does not occur in the SHR. Therefore, strips from older SHR rats are more reactive to ACh than are those from age matched WKY rats.Acknowledgment. The authors wish to acknowledge the assistance of Mark Kunneman and Elaine Hughes. This work was supported by the following grants: American Heart Association (Texas Affiliate) and National Institutes of Health HL 23815, HL 25349 and HL 24585.     

Forecasting Hong Kong's container throughput: an error‐correction model

A three‐player oligopoly model is devised to capture the competitive interaction between operators of the Hong Kong container terminals, the Hong Kong midstream and the Singapore container terminals in providing container handling services. The oligopoly model is then estimated statistically and thereby the structural parameters can be identified. The results of the estimation confirm a substitutability between the services supplied by operators of different types (terminal versus midstream) and different locations (Hong Kong versus Singapore). Moreover, the model proposed in this article generates forecasts of demand for Hong Kong's container handling services that are more accurate than those reported by the government authority, and suggests an earlier construction of new terminals to meet future demand. Copyright © 2002 John Wiley & Sons, Ltd.     

Changes with hypertension and maturation in the response of stomach fundus to acetylcholine

The purpose of these experiments was to compare the contractile response to ACh of stomach fundal strips from hypertensive (SHR) and normotensive (WKY) rats during the development of hypertension. The results indicate that the reactivity to ACh is the same in fundal strips from young SHR and WKY rats; however, with maturation strips from WKY rats undergo a reduction in responsiveness which does not occur in the SHR. Therefore, strips from older SHR rats are more reactive to ACh than are those from age matched WKY rats.     

Enhanced reactivity towards flunarizine in cerebrovascular bed of spontaneously hypertensive rats

Summary Cerebral blood flow (CBF) was measured and cerebrovascular resistance (CVR) was calculated in anesthetized spontaneously hypertensive rats (SHR) and normotensive rats (NR) following the administration of incremental dosages of i.v. flunarizine or papaverine. CBF and CVR changes following papaverine were the same in both groups of rats irrespective of the dose of the drug. The effect of flunarizine was much more pronounced in SHR than in NR. The results point out the greater dependency of basal cerebrovascular tone in SHR upon Ca²⁺ influx into vascular smooth muscle cells.     

Hydrocortisone administration enhances vessel contractility in Koltushi low-, and Koltushi high-avoidance rats

The contractility of tail artery rings was investigated in rats psychogenetically selected for rapid (KHA) and slow (KLA) acquisition of an avoidance response in the shuttle box. The vessel contractility was greater in the KHA rats. Hydrocortisone administration enhanced vessel contractility in both strains.     

Copper metabolism in the LEC rat: Involvement of induction of metallothionein and disposition of zinc and iron

The Cu concentration was about 40 times higher in the liver of LEC (Long-Evans with a cinnamon-like coat color) rats aged 77 days (227.5±21.6 g/g liver) than in Fischer rats (5.2±0.1 g/g liver). However, in the kidney and brain of the LEC rats, Cu concentrations were lower than in these organs of the Fischer rats. Cu concentration in the hepatic metallothionein fraction was about 130 times higher in the LEC rats than in the Fischer rats. The LEC rats showed markedly low concentrations of Cu in the serum and bile. It seems likely that excretion of Cu from the liver into the bile and blood (as ceruloplasmin) is inherently lacking in the LEC rat.     

Increase in Na+, K+ -ATPase enzyme units in liver and kidneys from essential fatty acid deficient rats.

(3H)-Ouabain binding to liver and kidney preparations was utilized to estimate the number of Na+, K+-ATPase enzyme units in livers and kidneys from rats fed 2% corn oil supplemented or fat-free diets. The specific (3H)-ouabain binding in liver and kidney preparations from fatty acid deficient rats was increased approximately 40%, but the affinity of the binding sites for ouabain (Kd-value) remained unchanged. The increased concentration of Na+, K+-ATPase enzyme units observed in the essential fatty acid deficient rats may contribute to the reduced body fat accumulation and elevated heat production observed in these animals.     

Effects of thyroidectomy and thyroxine replacement on the responsiveness of the anterior pituitaries from male rats to thyrotropin-releasing hormone in vitro

Summary Thyroidectomy decreased prolactin concentrations in the anterior pituitary (AP) and serum of the male rat. The amount of basal and thyrotropin-releasing hormone (TRH)-stimulated release of prolactin by AP in vitro was lower in thyroidectomized (Tx) rats than in sham Tx rats. These results suggest that the inhibitory effects of thyroidectomy on pituitary and serum prolactin in male rats are mediated in part by the reduction of the production and spontaneous release of prolactin and the responsiveness of prolactin to TRH.     

Long-term depressor effects of catecholamine neuronal grafts in the third ventricle of the brain in normotensive rats

Neuronal tissue containing A-6 group noradrenalin (NA) neurons of the locus ceruleus, or A-10 group dopamine (DA) neurons of the substantia nigra, was grafted into the third ventricle at the level of the preoptic-anterior hypothalamic region, in normotensive male rats. A significant and long-lasting depressor effect was shown in rats with either graft. In rats with an NA neuron-rich graft, plasma concentrations of arginine-vasopressin (AVP), plasma renin activity (PRA), and corticosterone (CS) decreased significantly, whereas in rats with a DA neuron-rich graft, AVP and PRA concentrations also decreased significantly but CS showed no significant change. Neither NA nor adrenalin in plasma changed significantly in rats with either graft.     

Synergism between long-acting bromocryptine microcapsules and cyclosporine A in the prevention of various autoimmune diseases in rats

Pre-treatment of male Sprague-Dawley rats with long-acting bromocryptine microcapsules (CBLA) significantly inhibited the arthritic response to Freund's complete adjuvant and reduced weight loss, thymolysis, splenomegaly and leukocytosis. In the prevention of adjuvant arthritis (AA), the combination of CBLA plus sub-optimal doses of cyclosporine A (CsA) was more efficient than either of the drugs alone. Sub-optimal doses of CsA were 0.1 and 1.0 mg/kg/day s.c. for 5 days. Furthermore, CBLA alone did not decrease the incidence of experimental allergic uveitis (EAU) in the male Lewis rats. Low-dose CsA reduced the incidence of uveitis by 50%, and with the addition of CBLA, 100% of rats were protected. Low-dose CsA was 2 mg/kg/day i.m. for 14 days. Long-term treatment of male Sprague-Dawley rats with CBLA alone reduced the incidence and severity of spontaneous autoimmune periateritis nodosa (PN) in a dose-dependent manner; CsA was less potent than CBLA, and only additive effects were obtained. Finally, for the prevention of spontaneous autoimmune insulin-dependent diabetes (DM), the administration of CBLA did not improve the effect of a low-dose CsA in male BB rats. Nevertheless, a delay in onset of DM could be achieved. A sequential therapy using CsA plus CBLA clearly showed beneficial effects. The dose of CsA was 10 mg/kg p.o. 6 days/week for 21 weeks. Compared with Sprague-Dawley or Lewis male rats, BB male rats showed only weak prolactin suppression after the same doses of CBLA. It is suggested that the use of CBLA may be particularly beneficial in autoimmune disorders. The effectiveness of the combination therapy CBLA plus CsA, however, was dependent on the model considered. Various factors could play a role: (1) the different ways of administering CsA (s.c. in AA, i.m. in EAU and PN, oral in DM); (2) strain-dependency in the capacity of CBLA to suppress Prl secretion; and(3) at least in the BB rats, the transient increase of CsA bioavailibility which was possibly induced by CBLA.     

Lasting effects of acute dehydration and post-weaning undernourishment on cortical spreading depression in adult rats

Summary Acute dehydration (D) early in life made adult rats less susceptible to cortical spreading depression (SD) than control (C) rats. Post weaning undernourished (U) rats tended to be more susceptible than controls. The association of D and U (DU group) made rats more susceptible to SD than U-rats. It is suggested that this association gives rise to a more complex pathological state than that which would result from the summation of the effects of its components.This work was supported by the Brazilian agencies CNPq and CAPES and by the Federal University of Pernambuco. The suggestions of Dr. T. P. Hicks, which contributed to improve the English text, are very much appreciated.     

Long-term depressor effects of catecholamine neuronal grafts in the third ventricle of the brain in normotensive rats

Summary Neuronal tissue containing A-6 group noradrenalin (NA) neurons of the locus ceruleus, or A-10 group dopamine (DA) neurons of the substantia nigra, was grafted into the third ventricle at the level of the preoptic-anterior hypothalamic region, in normotensive male rats. A significant and long-lasting depressor effect was shown in rats with either graft. In rats with an NA neuron-rich graft, plasma concentrations of arginine-vasopressin (AVP), plasma renin activity (PRA), and corticosterone (CS) decreased significantly, whereas in rats with a DA neuron-rich graft, AVP and PRA concentrations also decreased significantly but CS showed no significant change. Neither NA nor adrenalin in plasma changed significantly in rats with either graft.     

Vascular reactivity in chronic Goldblatt two kidney-one clip hypertensive rats

Summary We studied the possible contribution of increased vascular reactivity in the chronic phase of Goldblatt two kidney-one clip hypertension. Vascular reactivity was evaluated in aortic strips from hypertensive rats (16 weeks after inducing hypertension) and age-matched control rats. The findings were: a) increased sensitivity to vasopressin in the aortic tissue of hypertensive rats, b) a similar response to angiotensin II, noradrenaline and KCl in hypertensive and control rats, and c) reduced maximal response to angiotensin II compared with other vasoconstrictors in both groups of rats. These results suggest a possible role for vasopressin in the chronic phase of this model of hypertension.The authors thank Ms Karen Shashok for revising the English style.     

Vascular reactivity in chronic Goldblatt two kidney-one clip hypertensive rats

We studied the possible contribution of increased vascular reactivity in the chronic phase of Goldblatt two kidney-one clip hypertension. Vascular reactivity was evaluated in aortic strips from hypertensive rats (16 weeks after inducing hypertension) and age-matched control rats. The findings were: a) increased sensitivity to vasopressin in the aortic tissue of hypertensive rats, b) a similar response to angiotensin II, noradrenaline and KCl in hypertensive and control rats, and c) reduced maximal response to angiotensin II compared with other vasoconstrictors in both groups of rats. These results suggest a possible role for vasopressin in the chronic phase of this model of hypertension.     

Increased Na+-H+ exchanger activity in the ileal brush-border membrane of spontaneously hypertensive rats

In the present study, we have examined the intestinal Na⁺ transport, through the Na⁺-H⁺ exchanger, in ileal brush-border membrane vesicles (BBMV) isolated from spontaneously hypertensive rats (SHR), and normotensive Wistar Kyoto (WKY) rats as a control group. Na⁺ uptake into ileal BBMV was stimulated in the presence of a proton gradient (pH 5.5 inside/pH 7.5 outside) in SHR and WKY rats, resulting in a transient accumulation (overshoot) in both groups of rats. No overshoot was observed in the absence of a pH gradient. The magnitude of the accumulation was significantly higher in SHR than in WKY rats. Uptake of Na⁺ at equilibrium was identical in the presence and the absence of a proton gradient and was not changed in SHR. The use of amiloride inhibited pH gradient-driven Na⁺ uptake in a dose-dependent manner with a Ki of 90 μM and 100 μM for SHR and WKY rats, respectively. The relationship between proton gradient-driven Na⁺ uptake and external Na⁺ concentration was saturable and conformed to Michaelis-Menten kinetics in both SHR and WKY rats. Lineweaver-Burk analysis of the pH gradient-driven Na⁺ uptake indicated values of V_max that were significantly increased in SHR compared to WKY rats (11.4±0.55 nmol/mg/8 s vs. 4.96±0.78 nmol/mg/8 s for SHR and WKY rats, respectively). In contrast, similar K_m values for Na⁺ were found between SHR and WKY rats (4.0±0.2 mM vs. 4.9±0.6 mM for SHR and WKY rats, respectively). These studies show derangement in ileal BBMV Na⁺ transport of SHR, which is characterized by increased Na⁺-H⁺ exchanger activity. Received 18 December 1996; received after revision 3 February 1997; accepted 7 February 1997