摘要:

In all forms of chronic hypertension, the renal-pressure natriuresis mechanism is abnormal because sodium excretion is the same as in normotension despite the increased blood pressure. However, the importance of this resetting of pressure natriuresis as a cause of hypertension is controversial. Theoretically, a resetting of pressure natriuresis could necessitate increased blood pressure to maintain sodium balance or it could occur secondarily to hypertension. Recent studies indicate that, in several models of experimental hypertension (including angiotensin II, aldosterone, adrenocorticotrophic hormone, and norepinephrine hypertension), a primary shift of renal-pressure natriuresis necessitates increased arterial pressure to maintain sodium and water balance. In genetic animal models of hypertension, there also appears to be a resetting of pressure natriuresis before the development of hypertension. Likewise, essential hypertensive patients exhibit abnormal pressure natriuresis, although the precise cause of this defect is not clear. It is likely that multiple renal defects contribute to resetting of pressure natriuresis in essential hypertensive patients. With long-standing hypertension, pathological changes that occur secondary to hypertension must also be considered. By analyzing the characteristics of pressure natriuresis in hypertensive patients and by comparing these curves to those observed in various forms of experimental hypertension of known origin, it is possible to gain insight into the etiology of this disease.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Activation of renal dopamine-1 receptors decreases sodium transport. However, the spontaneously hypertensive rat retains sodium despite increased renal dopamine concentration. We tested the hypothesis that the abnormal sodium handling in spontaneously hypertensive rats (Okamoto-Aoki strain) is related to a decreased dopaminergic response by studying the effects of the intrarenal infusion of the dopamine-1 agonist SKF-38393 and the dopamine-1 antagonist SCH-23390 in hypertensive and in normotensive Wistar-Kyoto rats. Rats (9–16 weeks old) were studied with renal nerves intact under pentobarbital anesthesia (n= 5–6 in each group). Specificity of dopamine-1 effects of SKF-38393 was verified because its natriuretic effect was blocked in a dose-related manner by the dopamine-1 antagonist SCH-23390 (n= 5). Intrarenal arterial infusion of the dopamine-1 agonist SKF-38393 did not affect glomerular filtration rate but resulted in a dose-related natriuresis and diuresis in normotensive but not in hypertensive rats. Intrarenal arterial infusion of the dopamine-1 antagonist SCH-23390 alone induced an antinatriuresis, without affecting glomerular filtration rate, in normotensive but not in hypertensive rats. Addition of the dopamine-2 antagonist YM- 09151 to the dopamine-1 antagonist infusion did not enhance the effect of the dopamine-1 antagonist The lack of response to the dopamine-1 agonist or antagonist in hypertensive rats was not due to differences in renal dopamine-1 receptor density (U ± 0 J pmol/mg protein for spontaneously hypertensive rats, n=4; l±0.2 for Wistar-Kyoto rats, n=4) or affinity, distribution determined by autoradiography was also similar. The abnormal renal sodium handling in 9–16-week-old spontaneously hypertensive rats is in part due to decreased response distal to the dopamine-1 receptor.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

A familial predisposition to arterial hypertension has recently been suggested as one important component of the susceptibility to diabetic kidney disease. Sodium-lithium countertransport activity, a marker of risk for essential hypertension, has been found to be increased in diabetic patients with overt nephropathy. We have measured red blood cell sodium-lithium countertransport activity in 36 microalbuminuric insulin-dependent diabetic patients, a group at high risk of progression to clinical nephropathy and cardiovascular disease, and compared it with that of a matched group of 36 normoalbuminuric diabetic patients. Sodium-lithium countertransport was higher in the microalbuminuric (0.43 [95% confidence interval (CI) 0.38–0.47] mmol/l red blood cells [RBC]/hr) than in the normoalbuminuric diabetic patients (0.29 [0.25–0.33] mmol/l RBC/hr, mean difference 0.14 [0.08–0.20];p< 0.0001). Microalbuminuric patients had a higher frequency of parental hypertension than normoalbuminuric diabetic patients (56% vs. 28%,p< 0.05). Sodium-lithium countertransport was related to mean arterial pressure in the microalbuminuric patients (r=0.54,p< 0.001) and to daily insulin requirements in both groups (microalbuminuric patients r=0_39,p< 0.05; normoalbuminuric patients r=0.42,p< 0.01). In a subset of patients in whom lipoproteins were measured, sodium-lithium countertransport activity was related to total and very low density lipoprotein triglycerides (r=0.41,p< 0.05 and r=0.48,p< 0.05) and to apolipoprotein B (r=0.56,/?<0.05), independently of body mass index, albumin excretion rate, glycemic control, and insulin dose. Thus, an overactivity of sodium-lithium countertransport occurs in microalbuminuric insulin-dependent diabetic patients and is independently associated with a higher blood pressure and a more atherogenic lipoprotein profile.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Selective renal medullary destruction is produced in rats by a single injection of 2- bromoethylamine hydrobromide. The object of these studies was to investigate whether destruction of the renal medulla in normal rats would alter vascular capacitance. Conscious bromoethylamine-treated rats (n= 15) were compared with control saline-injected rats (n= 12). Mean circulatory filling pressure was measured during a brief circulatory arrest caused by inflation of a right atrial balloon. Blood volume was determined from plasma volume (iodine-125-labeled albumin) and hematocrit. Mean circulatory filling pressure was measured at resting blood volume and after rapid blood volume changes. Vascular compliance was derived from the mean circulatory filling pressure-blood volume curve. The bromoethylaminetreated rats were significantly hypertensive compared with control rats (mean arterial pressure 133±2 and 114±3 mm Hg, respectively,p< 0.001) and had a significant tachycardia (475±8 and 443 ±10 beats/min, respectively, p=0.02). Blood volume, plasma volume, hematocrit, and sodium excretion were no different There was no significant difference in mean circulatory filling pressure (6.5±0.2 and 6.8±0.2 mm Hg, respectively, p=0.4) or vascular compliance (3.64±0.20 and 3.53±0.12 ml/kg/mm Hg, respectively, p=0.7). The position of the vascular pressure-volume curve was unchanged indicating no change in vascular capacity. This would suggest that the destruction of renal medullary vasodepressor mechanisms does not result in alterations in vascular capacitance.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Earlier work with rat arteries has resulted in a widely held assumption that resistance artery smooth muscle will not contract on exposure to a reduced transplasmalemmal sodium gradient. In view of the well-recognized low sensitivity of rat tissue to cardiac glycosides, we have investigated the effects of altering the transplasmalemmal sodium gradient on vascular smooth muscle tone by using human resistance arteries. Incubation of arteries in low sodium or in ouabain to inhibit active sodium efflux for 1 hour increased the contractile response to caffeine stimulation; this finding indicated enhanced calcium buffering by the sarcoplasmic reticulum. Prolonged incubation in ouabain in the presence of phentolamine or diltiazem resulted in a concentration-dependent increase in the tone of resting human resistance arteries. Reduction of the transplasmalemmal sodium gradient by incubation in low sodium buffer effected an increase in tone similar to that obtained in the presence of ouabain. These results suggest that alteration of the transplasmalemmal sodium gradient may increase the vascular smooth muscle tone of human resistance arteries by altering intracellular calcium handling. This is a new finding in human resistance arteries and may involve inhibition and, indeed, reversal of sodium-dependent calcium efflux. A concentration-dependent potentiation of tone was found after the addition of ouabain to submaximally activated arteries. Sodium-calcium exchange may also play a pivotal role in this mechanism.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The present study was designed to study the functional properties of Angiotensin II (Ang II) binding sites in vascular smooth muscle cells in the Milan hypertensive rat (MHS), a model of low renin hypertension. Smooth muscle cells from MHS rats exhibited increased growth in culture in comparison with the Milan normotensive strain (MNS) as determined by population doubling times (24.5±2 and 34.8±2 hours, n=4, respectively). Hormone receptor number, evaluated by binding assays using [12SI]Ang II, showed no difference in either receptor number or affinity for both cell types. The functional responsiveness of Ang U receptors was evaluated by measuring the activation of phospholipase C, Na+-H+ exchange, and cytosolic Ca2+ levels. Phospholipase C activity was determined as tritium-labeled inositol trisphosphate and bisphosphate release before and after 15-second exposure to 10″7 M Ang II. Ang II-stimulated phospholipase C activity in MNS (p< 0.02) but not in MHS cells. Na+-H+ exchange was measured as the dimethylamiloride-sensitive nNa+ influx into acid-loaded vascular smooth muscle cells with and without 10″7 M Ang II. In MNS cells, Ang II significantly stimulated (/?< 0.001) antiporter activity but not in MHS cells, which showed a uniformly blunted response. MHS cells exhibited higher basal cytosolic Ca2+ levels than MNS cells, but Ca3+ rapidly increased in the presence of Ang II in MNS but not in MHS cells. Direct activation of phospholipase C by GTP-y-S in permeabilized cells indicated that both strains exhibited similar coupling levels by guanine-nucleotide binding proteins. In summary, cultured smooth muscle cells from MHS rats exhibit blunted phospholipase C, Na+-H+ exchange, and cytosolic Ca3+ responses to Ang II despite having the same number of Ang II receptors as MNS cells. This suggests that, in this model of low renin hypertension, Ang II receptor response is blunted during increased growth rates.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Using five sham-operated and seven aortic coarctation-induced hypertensive New Zealand White rabbits intravenously injected with neutral small unilamellar vesicles loaded with [“Inlnitrilotriacetic acid, we demonstrated in vivo that the normal aortic arterial wall participates in liposome uptake and that this uptake is increased in the hypertensive aortic wall by approximately threefold (p≤ 0.0001). Among the three regions examined, aortic arch, thoracic aorta, and lower abdominal aorta, the difference in uptake between the normotensive and hypertensive arterial walls was significantly different,p≤ 0.05,p≤ 0.0001, andp≤ 0.05, respectively. The uptake by the different regions of the hypertensive arterial wall is consistent with the pathological changes present in these areas. Furthermore, the extent of liposome uptake by the aortic wall is strongly correlated with the height of the blood pressure (r=0.85, p=0.001, n = 11). We conclude that neutral small unilamellar liposomes can be used to carry agents into the arterial wall in vivo in the study of hypertensive vascular disease and could be especially useful for the delivery of pharmacologically or biologically active agents that would otherwise be inactivated within the circulation or are impermeable to the arterial wall.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

There is controversy as to whether platelet intracellular free calcium ([Ca2+],) is increased in spontaneously hypertensive rats (SHR) as compared with Wistar-Kyoto (WKY) rats. Discrepant results may be due to methodological problems including platelet activation during the collection process and leakage of intracellular dye used for [Ca], measurement To provide further insight into this problem, [Ca2+], was estimated in fura-2-loaded platelets isolated from eight SHR and seven WKY rats at 12–14 weeks of age by using a two-syringe blood collection method and a correction method for fura-2 leakage. Basal [Ca2+], was higher in SHR than in WKY rats (61.6±5.6 vs. 54.0±3.9 nM,p< 0.02). However, the difference disappeared when a correction for fura-2 leakage was not used (109.7±18.4 vs. 94.9±9J nM, P>0.1). Thus, differences in [Ca2+], between SHR and WKY rats may be obscured if dye leakage from platelets is not taken into account Thrombin (0.1 units/ml) induced a rise in [Ca1+]t that was greater in SHR than WKY rats, both in the presence (491.4±31.6 vs. 377.5±21.7 nM,p< 0.002) and absence (264.9±33.6 vs. 228.2±30.1 nM,p< 0.05) of calcium in the media. These results indicate that thrombin-stimulated calcium influx as well as discharge of calcium from intracellular stores is increased in SHR platelets. Thus, under both basal and stimulated conditions, platelet calcium handling is abnormal in the SHR.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Blood pressure response to chronic high salt intake and kinetics of red blood cell Na+ and K+(Rb+) transport were studied in salt-sensitive (DS) and salt-resistant (DR) Dahl rats fed a high salt diet (8% NaCl) for 7 weeks from the fifth (young), 12th (adult), or 23rd (old) week of age. The kinetics of ouabain-sensitive Rb+ uptake and Na+ extrusion were determined in Na+ media as a function of both intracellular Na+ (Na+, 2–8 mmol/1 cells) and extracellular Rb+ (Rb+ 0). In addition, the kinetics of furosemide-sensitive Rb+ uptake (related to Rb+ 0) and the magnitude of the Na+ and Rb+ leaks were assessed. High salt intake induced hypertension in young and adult but not in old DS rats although red blood cell Na+ was slightly increased in all age groups of DS rats fed a high salt diet The kinetic parameters of the Na+-K+ pump were similar in DS and DR rats fed a low salt diet Ouabain-sensitive transport rates were not suppressed in erythrocytes of salt hypertensive Dahl rats. Maximal velocities of the Na+-K+ pump (related to Na+,) decreased significantly with age in all groups except in DS rats fed a high salt diet This was compensated by an age-dependent increase in the affinity for Na+, so that no substantial differences in transport rates between young and old rats were seen at physiological cell Na+ and plasma K+ levels. The maximal velocity of furosemide-sensitive Rb+ uptake rose with age in all groups without changes in the affinity for Rb+ 0. High salt intake increased its maximal activity only in DS rats. The Rb+ leak was higher in DS relative to DR rats irrespective of salt intake, age, or blood pressure. The Na+ leak was elevated in DS rats in which it was augmented by high salt intake. Salt hypertension was, however, not associated with a significant increase of the Na+ leak, which was responsible for most alterations of cell Na+ content.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The reduction in blood pressure to normotensive levels within 3 hours of unclipping the one-kidney, one clip Goldblatt hypertensive rat has been attributed to the release of potent blood pressure-lowering lipids, one of which is thought to be identical to platelet activating factor. The specific platelet activating factor receptor antagonist WEB 2086 was infused intravenously into hypertensive one-kidney, one clip rats, and the mean arterial blood pressure changes after unclipping were examined. Before infusion, blocking doses of WEB 2086 were confirmed to effectively abolish the fall in blood pressure induced by exogenous platelet activating factor. Serotonin release in response to exogenous platelet activating factor was also inhibited in platelets preincubated with plasma from rats infused with the antagonist Hypertensive rats were given a bolus blocking dose of WEB 2086 (5 mg/kg i.v.) and the same dose by infusion (5 mg/kg/hr i.v.) before they were undipped. A control group was given a bolus volume of saline and infused with saline before unclipping. In WEB 2086-treated rats, blood pressure fell from a baseline mean of 181 ±13.0 to 125 ±23 mm Hg after 4 hours, a fall of 28%. Saline-treated rats fell from a mean of 194±23 to 127±25 mm Hg (33%). There was no significant difference in the blood pressure fall between the two groups. Therefore, platelet activating factor is unlikely to be responsible for the restoration of normal blood pressure after unclipping the Goldblatt hypertensive rat We attribute the fall in blood pressure to other presently unidentified renomedullary lipids.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID