摘要:

SUMMARY Calcium handling by erythrocyte membranes was compared in genetically hypertensive (SHR) and normotensive (WKR) rats by direct measurement of calcium binding, passive influx, and adenosine triphosphate (ATP)-dependent extrusion. The SHR erythrocyte membranes exhibited the following abnormalities: 1) the binding capacity of the high affinity Ca2+-binding sites located on the inner side of the membrane was 0.84 ± 0.07 nmole/mg protein compared with 1.17 ± 0.08 nmole/mg protein in WKR, 2) ATP-dependent Ca2+extrusion, measured as the Ca2+influx into inside-out vesicles, was also lower than the WKR, as was the La3+-sensitive, Ca2+-dependent ATP hydrolysis, indicating reduced activity of the calcium pump; 3) the passive calcium influx into ATP-depleted red blood cells was slightly accelerated. These abnormalities in Ca2+binding and transport probably enhanced intracellular Ca2+concentration, and were observed under both prehypertensive and hypertensive conditions, in 3-week-old and adult SHR respectively. Similar membrane defects in excitable cells may help to explain the pathogenesis of hypertension, since they may increase vascular tone and/or catecholamine release.

ISSN:0194-911X    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SUMMARY Increased sympathetic nerrous system actirity has been demonstrated in established onekidney one dip hypertension in the rat. To determine the importance of the renal nerves in this model of hypertension, renal denervation or sham operation was carried out 2 weeks after clipping. Systolic blood pressure (BP) after clipping the renal artery In 27 nninephrectomlzed male Charles Rlrer rats increased significantly from 125 ± 3 mm Hg to a stable level of 185 ± 7 mm Hg by 2 weeks, in association with a positive sodium balance. Renal denervation in 13 animals resulted in a significant decrease in BP to 137 ± 7 mm Hg, while no change in BP was seen after sham operation in 14 »ntmal«-There was no difference in mean daily water intake, mean dally sodium intake, mean daily urine volume, or mean fractional urinary sodium excretion between sham-operated and renal-denervated animals during the 2 weeks after operation. Plasma renin activity (PRA) and creatinine clearance were not significantly different at sacrifice 2 weeks after operation. Six of the renaldenervated rats were followed for 11 weeks after surgery. The BP rose again to hypertensive levels (187 ± 8 mm Hg) by 5 weeks after renal denervation. Repeat renal denervation resulted in a significant decrease to 142 ± 8 mm Hg. Renal denervation in eight rats with established one-kidney Grollman hypertension (185 ± 8 mm Hg) also resulted in a significant decrease in systolic BP (143 ± 8 mm Hg). The data demonstrate the importance of intact renal nerves in the maintenance of hypertension in the one-kidney renal hypertensive rat. The depressor effect of renal denervation is not mediated by alterations in sodium intake or excretion, water intake or excretion, creatinine clearance or PRA.

ISSN:0194-911X    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SUMMARY The effects of Injection of a peptidase-reslstant analog of methionine-enkephalln, [D-Ala1]- raethionine-eokephalln, on blood pressure (BP), heart rate, and vasopressin release were studied in spontaneously hypertensive rats (SHR). Intravenous injection of [D-Ala'J-roethlonlne-eflkephalln (DAME) Increased BP in both SHR and normotenslve Wlstar-Kyoto (WKY) controls, with a significantly greater increase in hypertenslre rats. Intracerebrorentrtcular injection of DAME produced a Diphasic increase in BP and an increase in heart rate in both groups. The initial pressor effect was significantly greater in the SHR. Plasma vasopressin levels in SHR were depressed relative to both untreated hypertensive rats and animals given vehicle control injections. Intravenous pretreatment with a vasopressin vasopressor antagonist, [l-(β- mercapto-β-β-cyclopentamethyleneproplonlc acid)$-(0-methyl)tyroslne] arglnine-vasopressin, did not block either component of the central enkephalin response in hypertensive rats. These data indicate that central enkephalin injection does not release vasopressin and that SHR are hyperresponslve to enkephalin. It is concluded that pressor systems other than that of vasopressin mediate the enkephalin-induced cardiovascular effects.

ISSN:0194-911X    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SUMMARY To generate quantitative data relating to the potential hypertensive activity of arginlne vasopressin (AVP), 140 and 560 nV AVP/kg/min were infused chronically in both normotensive dogs and dogs made hypertensive by chronic infusion of either anglotensln II (AH) or aldosterone. The lower rate of AVP infusion increased plasma AVP concentration from 0.4 ± 0.1 to 6.0 ± 1.1 μU/ml. Mean arterial pressure (MAP) was recorded 24 hours per day, and all dogs were infused continuously with 800 ml of isotonic saline per day. During the initial days of AVP infusion in normotensive dogs, natriuresis, kalluresis, and water retention were prominent and MAP increased progressively to a peak on Day 6 (30 mm Hg above control). Subsequently, diuresis ensued, net water retention decreased, and MAP fell progressively to only 13 mm Hg above control by Day 12 of AVP infusion. In contrast, in AH or aldosterone hypertensive dogs during AVP infusion, the natriuresis was greatly attenuated, water balance was unchanged or even negative, and MAP either did not increase or increased only transiently. When AVP infusion was terminated in dogs given only AVP, diuresis occurred, and MAP fell gradually over a period of hours to hypotenslve levels. In marked contrast, cessation of AVP infusion in dogs with either AH or aldosterone hypertension was associated with a precipitous fall in MAP of 35 to 40 mm Hg within 1 hour; however, this reduction was only transient — over the subsequent hours, both salt and water retention occurred, and MAP returned to previous hypertensive levels. Thus, in the hypertensive models studied, high plasma levels of AVP had relatively weak hypertensive effects. Although variations in plasma AVP concentration were associated with rather pronounced acute effects on MAP, the long-term changes in MAP produced by AVP were either minimal or, in the case of the animals made hypertensive by other agents, nonexistent.

ISSN:0194-911X    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SUMMARY Blood pressure (BP) and heart rate became derated when prostaglandin E, (PGE2) was infused into the cerebral rentrides of awake and anesthetized rats. Frequency of sympathetic neural firing was also increased. While the magnitude of the pressor responses was larger In spontaneously hypertensive rats (SHRs) than in normotensive ones (NTRs), the accompanying increases in sympathetic nerve firing were not significantly different. Pressor effects were appreciable within 2 minutes after the start of the PGE2Infusion but did not become maximal until 15 minutes later. By contrast, acceleration in sympathetic nerve firing was maximal within 2 minutes and then dwindled or remained stationary thereafter. Removal of sympathetic vasomotor tone by cervical section of the spinal cord abolished early phases without affecting subsequent peaks of the pressor response. The overall height of the pressor responses In hypophysectomlzed NTRs was half that in sham-operated controls. These results suggest that PGE2acts centrally to elevate BP by increasing not only the sympathetic discharge but perhaps also the secretion of bypophysial hormones, such as vasopressln. In light of previous studies showing that SHRs secrete more vasopressln, It was considered possible that their enhanced pressor responsiveness to PGE2could result from a greater release of endogenous vasopressln.

ISSN:0194-911X    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SUMMARY Possible defects in blood pressure (BP) regulation were studied by recording responses to centrally-administered bradykinin. Pressor effects accompanied by increased sympathetic nerve activity were elicited by intracerebroventricular injections in intact rate, but significant differences between Kyoto-Wistar normotensive (KNR) and spontaneously hypertensive rats (SHR) were not detected. By contrast, intracarotid injections into cross-perfused head preparations consistently produced more prominent systemic effects in SHR than in KNR, and these differences became even more pronounced following carotid denervation. After destruction of central noradrenergic neurons in KNR by intracerebroventricular injection of 6-hydroxydopamlne (6-OHDA), responses to bradykinin became the same as those in SHR. These results are in accord with the interpretation that a-adrenergic mechanisms for Mood pressure regulation in supramedullary brain areas no longer function normally in SHR and that a similar dysfunction can be induced in KNR by pretreatment with 6-OHDA.

ISSN:0194-911X    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SUMMARY Sixteen patients with refractory hypertension were submitted to rigorous sodium depletion while cardloTascular bomeostasis was monitored with measurements of hormonal and bemodynamlc parameters and repeat saralasin tests. This regimen resulted in a negative sodium balance by an average of 300 mEq. The loss of sodium closely correlated to the decrease of body weight (r « 0.70,p< 0.005). Blood pressure (BP) decreased from 176/116 ± 8/3 to 155/109 ± 6/3 mm Hg. There was a significant correlation between percent increments in plasma renin activity (PRA) and the rise in plasma norepinephrine (r= 0.68,p< 0.05) and a dose negative correlation between percent increase in PRA and the ratio of fall in mean Mood pressure (MAP), per unit of weight loss (r= −0.73,p< 0.005). Thns, patients with the least percent increase In PRA demonstrated the greatest fall in BP per unit of weight loss, indicating that relative rather than absolute elevation of renin may be tne factor limiting antihypertenslve efficacy of sodium depletion. Sodium depletion induced increase in peripheral resistance and decrease in cardiac output, both mostly attributable to relative hyperreninemia. Indeed, the adverse hemodynamic changes were reversed by angiotensin inhibition, during which BP normalized. It is concluded that vigorous sodium depletion complemented by angiotensin blockade or suppression with sympatholytic agents improves management of otherwise refractory hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SUMMARY Cerebrospinal fluid (CSF) and plasma dopamine-beta-hydroxylase (DBH) actirity was measured in 22 normotensive (NT), 31 essential hypertensive (EH), and 11 renal bypertenslYe (RH) patients. Although no differences were observed in their plasma DBH, the mean CSF-DBH acthity and specific actirity of EH were significantly lower than those of NT and RH patients. Very low CSF-DBH (< 0.15 units/ml of CSF or < 0.5 unlts/mg of CSF protein) was found only in EH (26% of EH). Of the 31 EH patients, 19 (60%) had CSF-DBH activities lower than 0.5 units/ml, whereas only 5 of 22 NT (23%) and no RH fell within this range. Nevertheless, 20% of EH, 55% of NT, and 40% of RH patients had CSF-DBH activities above the mean value for NT (> 0.9 units/ml). NT subjects with very low plasma DBH (< 50 units/ml) had CSF-DBH activities that fell within normal range. With the exception of these subjects, the specific activity of CSF-DBH was always lower than that of the plasma enzyme.The concentration of albumin, alpha2beta, and gamma globulins was measured in plasma and CSF obtained from the last five NT, four EH, and two RH patients. A positive linear relationship was obtained when the log of the plasma/CSF concentration ratio for these proteins was plotted against their molecular weight. Similar slopes and intercepts were obtained for these patients, suggesting that no major differences seem to exist in their blood-brain-barrier permeability to proteins. The results suggest that measurements of CSF-DBH could be of help in the differential diagnosis of human hypertension and In the neurochemical characterization of EH. If CSF-DBH reflects central noradrenergic activity, its reduction might indicate the existence of a central catecbolamlnergic defect in a subgroup of EH patients.

ISSN:0194-911X    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SUMMARY Blood concentration and urinary excretion of captopril following SO mg oral administration were determined by high-performance liquid chromatography In normal subjects and patients with chronic renal failure. In normal subjects, the iwrimum blood concentration of the free form of captopril was obtained − within 1 hour and was not detectable after 6 hours; 41% of administered captopril was excreted into the urine as free form and metabolites within 2 hours, and 58% within 6 hours. In chronic renal failure patients with an average serum creatinine of 5.1 mg/dl, the absorption constant (Ka), maximum concentration (Cmax), and area under the blood concentration curre (AUC) were not significantly different from those in the normal subjects, but the elimination constant (Ke) and biological half-life (T1/t) showed a significant delay in the disappearance of captopril from the blood (p< 0.01 respectively). The cumulatire amount of urinary excretion of either free-form captopril or its' metabolites was significantly decreased at 2,4, and 6 hours in chronic renal failure patients (p< 0.01 or less, respectively). Impairment of kidney function is suggested to be an important factor In the promotion of blood retention of captopril.

ISSN:0194-911X    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

SUMMARY Antihypertensive polar renomedallary lipid (APRL), a conglomerate of l-0-alkyl-2-acetoylgtycero-3-pfaospbocboliiie analogs, was tested in 4- to 6-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats using mlcrodrculatory techniques. APRL (0.5 μg/ml), when added to the solution bathing the cremaster musde, caused significant changes in the diameter, red blood cell velocity, and blood flow In both groups of rats, for arterioles and venules. Arteriolar changes in diameter were significantly greater (p< 0.05) in SHR than in WKY. Mlcropipette application of APRL indicated a dosedependent response for arterioles and venules in both groups. Moreover, the potent nature of this compound was demonstrated. Relative potency of APRL given intravenously was tested in 10- to 12-weck-old SHR and WKY. Tbe response curve was shifted significantly to the left for SHR (p< 0.01). APRL interaction with known controllers of blood flow was tested in SHR. Blockade of cnolinergic, β-adrenergic, or histaminergic receptors did not inhibit APRL action. Blockade of prostaglandin or bradykinin synthesis did not prevent depression of blood pressure by APRL. APRL (40 μg/kg) inhibited (p< 0.001) the pressor response to norepinephrine (1-10 μg/kg) but not to angiotensin II (4 μg/kg)- The present study provides direct evidence that APRL is a vasodilator with increased potency in SHR hypertension. The acute vascular response may be mediated by alpha-adrenergic antagonism.

ISSN:0194-911X    

出版商:OVID    

年代:1981

数据来源: OVID