摘要:

External K+inhibits the maximal rate of outward Na+, K+cotransport in human red cells with no effect on the apparent affinity for internal Na+. The K+concentration giving halfmaximal inhibition (KIK) varied from 16 to 30 mM in 24 normotensive control subjects. Six of the 38 hypertensive patients showed a KIKabove the upper limit of this normal range. Only three hypertensive patients showed a KIKbelow normal range. The internal Na+content giving half-maximal stimulation of outward Na+, K+cotransport (KSNawas measured in the hypertensive patients (a normal range of KSNa= 9 to 16 mmol/liter cells was previously established in 50 normotensive control subjects). Eighteen hypertensive patients showed an abnormally high KSNa, as previously described in hypertensive patients whose Na+, K+cotransport system had a low affinity for internal Na+(Co⊖). Comparison of KSNa, with KIKshowed that all six hypertensive patients with high KIKand all three hypertensive patients with low KIKwere Co ⊖ hypertensive.

ISSN:0194-911X    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

We studied erythrocyte cation cotransport and countertransport systems in 21 and 27 patients with essential hypertension, respectively, all of whom were under 50 years of age, had a diastolic blood pressure level greater than 100 mm Hg, and had a family history of hypertension. The following parameters were normal in nearly all patients: total erythrocyte Na+and K+concentrations, the maximal rate (Vmax) of inward cotransport, the affinity of cotransport with Rb+as the substrate, the net outward cotransport of Na+ions, the passive “leak” influx of Rb+and the maximal rate of Li+-Na+countertransport. Only four patients gave clearly abnormal results; in two the maximal rate of both cotransport and countertransport was double the normal values, while another two patients demonstrated a greater than twofold increase in passive “leak” influx to Rb+ions. Most of the patients with moderate to severe essential hypertension in this Australian study were characterized by normal erythrocyte cation fluxes, but a few showed elevation of both cotransport and countertransport of cations.

ISSN:0194-911X    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

It has been postulated that depressed membrane sodium transport is a necessary step in blood pressure elevation in essential hypertension. Accordingly, leucocyte sodium efflux-rate constants were estimated in 14 normotensive subjects who had one or more first-degree relatives with essential hypertension, and also in 14 matched control subjects with no such family history, before and after taking bendrofluazide for 7 days. Efflux rates in the controls did not change after the diuretic. However, in the relatives, mean total sodium efflux-rate constant was at first significantly depressed but later rose to normal with the diuretic. This was due almost entirely to an increase in glycosidesensitive sodium pump activity. Blood pressure remained unchanged in both groups. Thus, assuming that perturbations in leucocytes reflect similar abnormalities in other cell lines, major changes in sodium transport in the normotensive individual without accompanying changes in blood pressure suggest that, while these changes may be a marker for later hypertension, they do not participate directly in blood pressure control.

ISSN:0194-911X    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Spleen cells from mice immunized with partially purified hog kidney renin were fused with mouse myeloma cells to produce a stable monoclonal hybridoma cell line that synthesizes an antibody against renin. A single monoclonal antibody was chosen for study and has been produced in large quantity and purified by affinity chromatography on protein A-Sepharose. The antirenin, which belongs to the IgG1subclass, exhibits anticatalytic activity against both hog and rabbit renin. An immunoafflnity column prepared from antibody coupled to Sepharose has been used in the purification of renin from hog kidney. Although renin is quantitatively adsorbed from solution, it can be eluted from the column under gentle conditions. The highly purified renin, with specific activity of 2122 Goldblatt Units/mg protein, exhibits both charge (pH 4.1 to 5.1) and size (38,000 to 42,700) heterogeneity. Hog kidney renin dissociates in the presence of sodium dodecyl sulfate (SDS) and mercaptoethanol to heavy and light chains with molecular weights of 33,700 and 5,800, respectively. In the presence of SDS, a small amount of a new form of renin is observed with a molecular weight of 19,500 which retains activity on renaturation. The monoclonal antibody should be a useful tool for the study of the renin-angiotensin system and especially for the purification of renin. The hybridoma cell line used in this study (F-32 VIII C4) has been donated to the American Type Culture Collection.

ISSN:0194-911X    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Investigations were performed on components of the renin-angiotensin system (RAS) in homogenate extracts of vascular tissue and aortic smooth muscle cells cultivated in vitro. Determinations of isoelectric points and pH optima indicated the existence in aortic homogenate extracts of two local angiotensin I (AI)-forming enzymes (AIFE) that were different from those of plasma, renal cortex, veins, and aortic smooth muscle cells. The pH optima for Al-converting enzyme (ACE) from vascular tissues, aortic smooth muscle cells, and plasma were in the same range (pH 8.0–8.5), and in agreement with those measured previously in other tissues. In contrast, in vitro studies with the ACE inhibitors MK-421 and MK-422 and measurement of isoelectric points suggested that aortic ACE was different from the plasma enzyme. AIFE and ACE activities were found to be elevated in spontaneously hypertensive rats (SHR). The biochemical characteristics of the enzymes investigated in the vascular tissue of SHR were not different from those of the normotensive controls. AI- and All-degrading enzymes were found both in aortic tissue and in aortic smooth muscle cells. One potent Al-degrading enzyme different from ACE was observed in aortic tissue. A high ratio of AI/AII immunoreactivities in arterial walls suggests the availability of renin substrate, and that Al-degrading enzymes are the rate-limiting enzymes for AH formation. The results further support the concept of an intrinsic vascular RAS.

ISSN:0194-911X    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

The relationship of active renin and inactive renin (trypsin-activated angiotensin- I-forming enzyme) to sodium depletion was examined in renal and peripheral plasma and at the subcellular level in the kidneys of dogs. Subcellular fractionation was carried out by discontinuous sucrose density (1.5 and 1.6 M) centrifugation. Sodium depletion selectively caused a six- to sevenfold increase in the renal content of inactive and active renins in the original homogenate, while the subcellular distribution patterns of these enzymes were little changed. Of the total granule fractions of 1.5 M sucrose (Fl), 1.6 M sucrose (F2), and sediment (F3), approximately 80% of inactive renin was recovered in Fl, which was rich in microsomes, while about 50% of active renin was in F2. The ratio of inactive to active renin was 0.02 in Fl and 0.003 to 0.004 in F2. Sodium depletion also caused a 20-fold increase in active renin and a twofold increase in inactive renin in peripheral plasma. The renal venous-arterial concentration difference of inactive renin was statistically significant in lowsodium dogs, although it was not significant in controls. The ratio of inactive to active renin was 0.2 to 0.4 in plasma from low-sodium dogs, while it was 1.5 to 3 in plasma from control dogs. These results suggest that plasma inactive renin originates, at least in part, in the kidney.

ISSN:0194-911X    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

In conscious rats with near-malignant phases of DOCA-salt (DS) hypertension, hemodynamics were studied with microspheres before and after administration of a vasopressin (VP) vasopressor antagonist in relation to plasma VP levels (pVP). Compared to the controls, the DS rats showed significant elevations in mean arterial pressure (MAP), total vascular resistance (TVR), and pVP, and a flow redistribution from kidney and spleen to skeletal muscles and heart, with increased vascular resistance in almost all organs. The antagonist elicited no significant systemic hemodynamic effects in DS rats as a whole; however, two subgroups, responders vs nonresponders, were identified according to the effects on MAP. In responders with a pVP of 29.2 ± 2.7 (SE) pg/ml, the antagonist lowered MAP (− 24.9 ± 5.9 mm Hg) and TVR significantly, while in nonresponders with a pVP of 15.2 ± 3.4 pg/ml, there were no effects. The major antagonist-induced regional responses were increased flow and decreased vascular resistance in skeletal muscles and skin in whole DS rats, and additionally in the gastrointestinal tract, portal organs, and testes in the responders. Significant correlations were observed between pVP, MAP, TVR, and depressor responses to the antagonist only when all data for DS and control rats were pooled. Thus, the systemic hemodynamic effects of VP are important only in responders with exceedingly elevated pVP. VP contributes significantly to the regional hemodynamic abnormalities in skeletal muscles and skin in whole DS rats, and also in several other organs in the responders.

ISSN:0194-911X    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

The purpose of this study was to determine the microvascular characteristics that cause cerebral cortical blood flow autoregulation to shift to a higher range of arterial pressures during established hypertension in spontaneously hypertensive rats (SHR). An open-skull technique with constant suffusion of artificial cerebrospinal fluid (PO2= 40–45 mm Hg, pCO2= 40–45 mm Hg, pH = 7.35–7.45) was used to view the parietal cortex of 18- to 21-week-old SHR and Wistar Kyoto (WKY) normotensive control rats. The resting inner diameters of first (1A)-, second (2A)-, and fourth (4a)- order arterioles were significantly (p< 0.05) smaller, and the wall thickness/lumen diameter ratios were significantly (p< 0.05) larger in SHR compared to WKY. Only 1A and 4A had significantly (p< 0.05) increased vessel wall cross-sectional area in SHR. At the resting mean arterial pressures of WKY and SHR, the passive (10−4M adenosine, topical) diameters of comparable types of arterioles were not significantly different (p> 0.05). At reduced arterial pressures, however, the arterioles in SHR had smaller maximum diameters than in WKY. Cortical blood flow in WKY and SHR was constant at arterial pressures from 70–150 mm Hg and 100–200 nun Hg, respectively. Resting arteriolar pressures in 1A, 2A, and 3A of SHR were substantially and significantly (p< 0.05) elevated, although pressures in the smallest arterioles and venules of WKY and SHR were similar. Therefore, it is possible that cerebral capillary pressure is only slightly elevated, if at all, in SHR as a result of the vasoconstriction. The number of arterioles per unit area of brain surface at rest was equal in WKY and SHR. In addition, the number of vessels was equal in WKY and SHR during maximal dilation, and neither type of rat demonstrated an opening of previously closed vessels upon maximum dilation. Therefore, the cerebral arteriolar constriction in SHR, which was probably potentiated by vessel wall hypertrophy of the largest and smallest arterioles, was the major contributor to an upward shift in the autoregulatory range, the protection of exchange vasculature pressures, and the increase in vascular resistance.

ISSN:0194-911X    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Fractional excretion of lithium, as a marker for proximal sodium reabsorption, was determined in normotensive Dahl S rats (susceptible to NaCI hypertension) and Dahl R rats (resistant to NaCI hypertension) before and following an acute sodium load. Baseline mean arterial pressures, inulin clearances, sodium excretion rates, and fractional lithium clearances were not different between the R and S rats. Following the salt loading and despite similar mean arterial pressures and degree of volume expansion, the glomerular filtration rate, urinary flow rates, and absolute sodium excretion rates were greater in R than S rats. The fractional excretion of lithium was also greater in R than S rats. These data demonstrate that, at equal mean arterial pressures, Dahl S rats have a reduced capacity for sodium excretion, and that this defect is present prior to the development of hypertension. Furthermore, the observation that these animals also have a lower fractional lithium excretion during volume expansion suggests that salt loading reduces proximal tubule reabsorption to a lesser extent in Dahl S than R rats. These data suggest that the subnormal sodium and water excretion observed after sodium loading in S rats may be partially due to an abnormality in proximal tubule sodium handling.

ISSN:0194-911X    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Acute subcutaneous (s.c.) administration of aldosterone increases ex vivo22Na efflux from rat tail artery smooth muscle, which appears to be due to a specific action on mineralocorticoid receptors. Indeed, this effect is blocked by the antimineralocorticoid compounds RU 28318 [17ß- hydroxy-3-oxo,7 α-propyl(17 α)-pregn 4-ene, 21 potassium carboxylate] and spironolactone. The specific glucocorticoid receptor agonist RU 26988 [11ß,17ß-dihydroxy-17-(l- propynyl) androesta- 1,4,6 trien-3-one] does not modify22Na efflux. We show here that aldosterone has, at physiological concentrations, a mineralocorticoid specific stimulating effect on passive and sodium pump dependent transmembrane movements of sodium from the rat tail artery smooth muscle. Aldosterone exerts two types of action on sodium transport: 1) a delayed stimulation of ouabain-dependent22Na efflux and ouabaln-independent22Na efflux, which are completely blocked by actinomycin D; and 2) a very rapid increase of passive22Na efflux, which is insensitive to actinomycin D and therefore does not seem to depend on transcription of genomk information.

ISSN:0194-911X    

出版商:OVID    

年代:1984

数据来源: OVID