β-alanine and α-L-alanine inhibit the exploratory activity of spontaneously hypertensive rats

Summary 1% -alanine and -L-alanine, when given for 7 days as the only drinking fluid, inhibited the exploratory activity of adult male spontaneously-hypertensive rats (SHR)_but not that of the normotensive Wistar-Kyoto rats (WKR). -Alanine decreased the taurine level in the liver of both strains and in the platelets of SHR. -Alanine decreased the taurine level in the liver of WKR and in the platelets of SHR.This study was supported by the Sigrid Jusélius Foundation.     

Dopamine-beta-hydroxylase activity in stroke-prone spontaneously hypertensive rats

Dopamine-beta-hydroxylase (DBH) activity was higher in the serum, the mesenteric artery and the cerebral cortex of 4-week-old stroke-prone spontaneously hypertensive rats (SHRSP), and lower in the nucleus tractus solitarii than it was in spontaneously hypertensive rats (SHR).     

Decreased monosaccharide transport in renal brush-border membrane vesicles of spontaneously hypertensive rats

Na(+)-dependent D-glucose and D-galactose transport were studied in brush-border membrane vesicles (BBMVs) from kidney cortex isolated from both spontaneously hypertensive rats (SHR) and their normotensive genetic control Wistar-Kyoto (WKY) rats. Initial rates and accumulation ratios of Na(+)-dependent D-glucose and D-galactose transport were significantly lower in SHR compared with WKY, the observed decreases being similar for both substrates. To explain the reduction in sugar transport by renal BBMVs, the density of Na(+)-dependent sugar cotransporters was studied in BBMVs from kidney cortex isolated from SHR and WKY rats. Phlorizin-specific binding and Western blot analysis indicated a reduction in the density of the cotransporters in SHR relative to WKY rats. This reduction was similar to those found for the initial rates and accumulation ratios for D-glucose and D-galactose in SHR. Na+ uptake, studied using 22Na+, was significantly increased in SHR, so the observed reduction in sugar transport could be due to disruption of the Na+ gradient between renal BBMVs in SHR. Furthermore, a significant decrease in the activity of Na(+)-K(+)-ATPase was observed in SHR. In conclusion, changes in the density of the Na(+)-dependent sugar cotransporter and in the Na+ gradient across the brush-border membranes might be involved in the observed reduction in sugar transport by renal BBMVs from SHR.     

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.     

Characterization of D-fructose transport by rat kidney brush-border membrane vesicles: changes in hypertensive rats

D-fructose transport was characterized in renal brush-border membrane vesicles (BBMVs) from both spontaneously hypertensive rats (SHR) and normotensive genetic control Wistar-Kyoto (WKY) rats. Kinetic studies indicated that the maximal rate (Vmax) of D-fructose transport was significantly lower in SHR compared with WKY rats. No differences were observed in the Michaelis constant (Km) or the diffusion constant (Kd) between the two groups of animals. D-fructose inhibited its own transport, whereas the presence of D-glucose, D-galactose, phlorizin, and cytochalasin B did not inhibit the transport of D-fructose in either animal group. To explain the reduction in D-fructose transport in SHR, the density of the D-fructose transporter, GLUT5, was analyzed by Western blot. GLUT5 levels were lower in SHR, a reduction similar to that of the Vmax. Thus, there appears to be a high-affinity, low-capacity, GLUT5-type fructose carrier in the apical membranes of rat kidney cortex, and the decrease in the Vmax of D-fructose transport in renal BBMVs from hypertensive rats correlates well with a reduction in the expression of GLUT5 protein.     

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.     

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.     

Dopamine-β-hydroxylase activity in stroke-prone spontaneously hypertensive rats

Summary Dopamine--hydroxylase (DBH) activity was higher in the serum, the mesenteric artery and the cerebral cortex of 4-week-old stroke-prone spontaneously hypertensive rats (SHRSP), and lower in the nucleus tractus solitarii than it was in spontaneously hypertensive rats (SHR).The authors wish to thank Prof. Masao Sano (Nagoya University) for his aid in dissecting the nucleus tractus solitarii and the locus coeruleus.     

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     

Effects of neurochemical lesions restricted to spinal cord monoaminergic neurons on blood pressure and sympathetic activity of spontaneously hypertensive rats

Intraspinal (i.s.) injection of 6-hydroxydopamine or 5,7-dihydroxytryptamine in newborn spontaneously hypertensive rats (SHR) resulted, in the adult animal (30-week-old), in a marked decrease of spinal cord noradrenaline (NA) or 5-hydroxytryptamine (5-HT) levels, respectively. Since both neurotoxin- and vehicle-injected rats developed full hypertension and had similar plasma catecholamine concentrations, it is concluded that in SHR neither spinal cord NA nor 5-HT play a major role in development and maintenance of hypertension.     

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.     

Selective activation of noradrenergic neurons in the brainstem and spinal cord of young spontaneously hypertensive rats

Summary In young spontaneously hypertensive rats (SHR), dopamine -hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) activities were examined in the brainstem nuclei. Activation of noradrenergic neurons in the locus coeruleus, A2 and spinal intermediolateral cell areas, resulting in enhanced sympathetic nervous activity in the periphery, initiates hypertension. Adrenergic neurons, unchanged in these and A1 cell areas of young SHR, are not involved in the development of hypertension in SHR.     

Decrease in [3H]ouabain binding sites in heart and brain from spontaneously hypertensive rats

Summary A decrease in the number of binding sites (B_max) for [³H]ouabain was observed in the heart (37%) and the brain (22%) of spontaneously hypertensive rats (SHR) when compared with age-matched control Wistar Kyoto rats. No variation was detected in the affinity constant (K_D).     

Central influence of vasopressin on baroreceptor reflex in normotensive rats and its lack in spontaneously hypertensive rats (SHR)

Summary In normotensive Wistar rats intracerebroventricular (i.c.v.) injection of 30 mU of lysine⁸-vasopressin enhances significantly the cardiovagal reflex bradycardia induced by a blood pressure rise. This effect is absent in spontaneously hypertensive rats (SHR) of the Okamoto strain.     

Monoamine oxidase inhibition by d-amphetamine in ganglia and nerve endings

Summary The inhibition of monoamine oxidase (MAO) activity by d-amphetamine was measured in homogenates of cat superior cervical ganglion and nictitating membrane, using tyramine (TM) and noradrenaline (NA) as substrates. In both tissues, d-amphetamine was shown to be a competitive inhibitor of the oxidation of TM. The Ki for d-amphetamine, as a MAO inhibitor, was lower in the ganglia than in the peripheral nerve endings.Supported by a Contract from the National Research Council of Argentina (CONICET) (Res. 67/79).     

15-Hydroxyprostaglandin dehydrogenase and hexokinase in spontaneously hypertensive rat kidney

Summary 15-Hydroxyprostaglandin dehydrogenase (PGDH) surged in hypertensive (SHR) and normotensive (WKY) rat kidney at 8 days of age, is greatest in SHR. Hexokinase fell in SHR at 17 days of age, but thereafter was similar to WKY. This suggests multisystem enzymatic abnormalities in SHR kidney during development of hypertension.     

Distribution of type A and B monamine oxidase activities in the central nervous system of rat and chick.

The distribution of type A and B monamine oxidase (MAO) activities in the central nervous system (CNS) of rat and chick was investigated using 5-hydroxytryptamine and beta-phenylethylamine as specific substrates. The distribution of type A MAO was similar to that of type B MAO in rat CNS, but quite different in chick CNS. This may be ascribed to the difference in animal species. The major part of MAO activity in the spinal cord was found to be type A.     

Some extracellular matrix elements as markers of 'capillary tunnels' in hypertrophied rat heart.

We studied the distribution of the extracellular matrix proteins fibronectin (FN) and laminin (LM) in the hypertrophied hearts of spontaneously hypertensive rats (SHR), using an immunofluorescence method with specific antibodies. The immunohistochemical reaction was positive in the cytoplasm of some hypertrophied cardiomyocytes. The results showed that FN and LM can be used as markers for tunnels, i.e. intracardiocytic invaginations of the sarcolemma. The tunnels observed contained capillaries.     

Intravital measurement of arteriolar pressure and tangential wall stress in normotensive and spontaneously hypertensive rats (established hypertension)

Summary Under intravital conditions, intravascular pressures of mesenteric resistance vessels were measured in normotensive (NR, mean blood pressure 92 mm Hg) and spontaneously hypertensive rats (SHR, 161 mm Hg) being elevated over all by about 75%; the tangential wall stress (=p·r/h; p represents the intravascular pressure and r/h the ratio of internal radius to wall thickness) was found to be increased by 120–140% in SHR.Supported by the DFG.     

Some extracellular matrix elements as markers of ‘capillary tunnels’ in hypertrophied rat heart

We studied the distribution of the extracellular matrix proteins fibronectin (FN) and laminin (LM) in the hypertrophied hearts of spontaneously hypertensive rats (SHR), using an immunofluorescence method with specific antibodies. The immunohistochemical reaction was positive in the cytoplasm of some hypertrophied cardiomyocytes. The results showed that FN and LM can be used as markers for tunnels, i.e. intracardiocytic invaginations of the sarcolemma. The tunnels observed contained capillaries.