Carotid back pressure following bilateral carotid occlusion in normotensive and spontaneously hypertensive rats

Summary In SHR, CBP fell markedly and remained below 50 mm Hg after carotid occlusion despite SBP being elevated, while in NTR changes in CBP were related with changes in SBP. Vascular resistance of the brain in hypertensive rats is discussed.     

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.     

Adenosine is a sensitive oxygen sensor in the heart

Cardiac adenosine is formed both by an oxygen-sensitive (AMP----adenosine) and by an oxygen-insensitive (S-adenosylhomocysteine----adenosine) pathway. The phasic adenosine release during beta-adrenergic stimulation with isoproterenol is closely linked to coronary venous PO2 (isolated heart) and can be almost fully prevented when diastolic aortic pressure is maintained constant (heart in situ). During pressure autoregulation the transmural gradient of free adenosine is only increased when the autoregulatory reserve is exhausted. The critical PO2 below which adenosine formation is enhanced was found to be 3 mm Hg (isolated cardiomyocytes). Collectively, these data indicate that the formation of adenosine is not primarily coupled to the energy expenditure of the heart but to the supply/demand ratio for oxygen.     

Reduced deformability of erythrocytes exposed to hypercapnia.

The effect of hypercapnia on the deformability of erythrocytes was studied by means of a nuclepore membrane filter method. A decrement of the deformability by 20--40% was observed when PCO2 was increased from 50 mm Hg to 200 mm Hg, accompanied with an increment of 5% in hematocrit value.     

A microanalysis of colloid osmotic pressure

Summary A needle type of colloid osmometer has been devised with special attachments which made it useable with 3-l samples. It has been used in oncometry of fresh water teleosts to give the following results: 5.1±1.0 mm Hg for goldfish, 5.2±0.71 mm Hg for carp, and 14.3±0.75 mm Hg for eel.This study was supported in part by Research Grant 387036 from the Ministry of Education of Japan.invited to National Institute of Physiological Sciences, Okazaki, Japan.     

Transmural pressure as a determinant of basic intrinsic heart rate

Summary It was observed the heart rate was minimum at zero transmural pressure. The mean heart rate at zero transmural pressure was 23±5/min. This mean heart rate increased from 23±5/min to a peak value of 40±6/min (74% acceleratin) when the transmural pressure was raised from 0 to +4 mm Hg and to a similar peak value of 36±8/min (56% acceleration) when the transmural pressure was lowered from 0 to –4 mm Hg. The peak values attained at ±4 mm Hg were higly significant (p<0.001). It is concluded that the heart rate at zero transmural pressure represents the basic intrinsic pacemaker frequency independent of neural, humoral, thermal and haemodynamically induced mechanical influences.     

Reduced deformability of erythrocytes exposed to hypercapnia

Summary The effect of hypercapnia on the deformability of erythrocytes was studied by means of a nuclepore membrane filter method. A decrement of the deformability by 20–40% was observed when was increased from 50 mm Hg to 200 mm Hg, accompanied with an increment of 5% in hematocrit value.     

The oxygen-linked hydrogen ion binding (the Haldane coefficient) of bovine hemoglobin.

The Haldane coefficient (the amount of the oxygen-linked hydrogen ion binding of hemoglobin) was determined in bovine erythrolysate (Hb concentration equals 13.5 mM) by means of the differential titration method with varying PCO2 from 0 to 74 mm Hg and pH from 6.0 to 8.5 at 37 degrees C. The maximum value of the coefficient was found to be 0.49 mM per mM Hb at PCO2 equals 0 and pH 7.20. With increasing of PCO2, the coefficient became smaller in all ranges of pH studied. The coefficient under the conditions of pH 7.20 and PCO2 equals 45 mm Hg that are normally prevailing in the interior of bovine erythrocytes was 0.31.     

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.     

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.     

Neurotrophin signaling: many exciting surprises!

Neurotrophins are growth factors implicated in the development and maintenance of different neuronal populations in the nervous system. Neurotrophins bind to two sets of receptors, Trk receptor tyrosine kinases and the p75NTR receptor, to activate several different signaling pathways that mediate various biological functions. While Trk receptor activation has been well-studied and triggers the well-characterized Ras/Rap-MAPK, PI3K-Akt, and PLCgamma-PKC cascades, p75NTR signaling is more complex, and its in vivo significance has not yet been completely determined. In the last few years, p75NTR has received much attention mainly due to recent findings describing pro-neurotrophins as new ligands for the receptor and the ability of the receptor to form different complexes with other transmembrane proteins. This review will update the neurotrophin signaling pathways known for Trk receptors to include newly identified Trk-interacting molecules and will address surprising new findings that suggest a role for p75NTR in different receptor complexes and functions.     

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.     

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     

Auto-oxidation of hemoglobin in plasma.

The rate of auto-oxidation of human hemoglobin to methemoglobin was measured in plasma at 37 degrees C. Half-lives of hemoglobin were found to be 20 h, 12 h and 7 h at the oxygen tensions of 126, 57 and 23 mm Hg, respectively.     

Bayliss myogenic response in the isolated ductus arteriosus of guinea-pig and rabbit fetuses

Summary Isolated ductus arteriosus responds by marked constriction to increases in perfusion pressure. If, however, these increases exceed 90 mm Hg-130 mm Hg, the vessel suddenly dilates and its responsiveness becomes depressed. The importance of these findings in postnatal closure of ductus arteriosus is discussed.     

Auto-oxidation of hemoglobin in plasma

Summary The rate of auto-oxidation of human hemoglobin to methemoglobin was measured in plasma at 37°C. Halflives of hemoglobin were found to be 20 h, 12 h and 7 h at the oxygen tensions of 126, 57 and 23 mm Hg, respectively.     

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.     

Difference of the inhibitory action of verapamil on the positive inotropic effect of Ca2+ between spontaneously hypertensive and normotensive rat myocardium

Verapamil, a calcium entry blocker, had a greater inhibitory effect on the positive inotropic effect of excess Ca2+ in SHR than in NWR, suggesting that the cardiac responsiveness to verapamil was enhanced in SHR.     

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.     

Difference of the inhibitory action of verapamil on the positive inotropic effect of Ca2+ between spontaneously hypertensive and normotensive rat myocardium

Summary Verapamil, a calcium entry blocker, had a greater inhibitory effect on the positive inotropic effect of excess Ca²⁺ in SHR than in NWR, suggesting that the cardiac responsiveness to verapamil was enhanced in SHR.