ISSN:0194-911X    

出版商:OVID    

年代:1987

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1987

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Abnormalities in the vasopressin and renin systems have been reported in spontaneously hypertensive rats (SHR). Therefore, studies were performed to evaluate the responsiveness of these systems to changes in plasma osmolality and sodium concentration. These variables were manipulated in vivo by intraperitoneal administration of distilled water, isotonic saline, or hypertonic saline to 8- and 18-week-old SHR and normotensive Wistar-Kyoto rats (WKY). Animals were decapitated 30 minutes later, and trunk blood was collected. The hypertonic saline injections resulted in an increase in plasma osmolality and serum sodium at both ages (p< 0.001). Serum vasopressin was higher in all groups of animals receiving hypertonic saline (1200 mosm/kg H2O;p< 0.05), but the magnitude of increase was not significantly different in the SHR and WKY at either age. Serum renin activity was lower in SHR than in WKY following acute decreases in serum sodium at 8 weeks, but it was the same for both strains at 18 weeks. Both kidney renin content and concentration were lower in SHR than in WKY at 18 weeks but not at 8 weeks. Therefore, the suppressed renin response to acute osmotic challenge in 8-week-old SHR is not the consequence of reduced kidney renin content. The vasopressin response to osmotic stimulation also was evaluated in vitro using hypothalamoneurohypophyseal explants obtained from 5-, 8-, and 18-week-old SHR and WKY. Vasopressin release was significantly increased in response to an increase in osmolality of 12 mosm/kg H2O in all groups (p< 0.01), but the response was not significantly different in explants of SHR and WKY at any age. The comparable response of the vasopressin system to osmotic challenge in SHR and WKY is in contrast to the previously observed hyperresponsiveness of the vasopressin system to an acute decrease in plasma volume and to acetylcholine in vitro. Thus, it indicates that the previously observed hyperresponsiveness of the vasopressin system is specific to the stimulus rather than a generalized phenomenon.

ISSN:0194-911X    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Recent studies from this laboratory have demonstrated that 19-nor-deoxycorticosterone, a potent mineralocorticoid, has been excreted in excess in the urine of young spontaneously hypertensive rats (SHR). Although urinary 19-nor-deoxycorticosterone levels decline before the onset of hypertension, preliminary evidence suggests that 19-nor-deoxycorticosterone is further oxygenated to other steroid products in older SHR. Since 19-hydroxylation is the essential first step in the formation of 19-nor-deoxycorticosterone from deoxycorticosterone and since the mechanism-based aromatase inhibitor 10-propargyl-androst-4-ene,3,17-dione preferentially inhibits 19-hydroxylation, this agent was administered to weanling SHR to determine whether inhibition of 19-nor-deoxycorticosterone formation could modify or prevent hypertension. Accordingly, either 10 mg of 10-propargyl-androst-4-ene,3,17-dione or vehicle (control) was injected daily for several weeks in 4.5 week-old SHR. Injection of 10-propargyl-androst-4-ene,3,17-dione reduced urinary free 19-nor-deoxycorticosterone and retarded the development of hypertension compared with the effect of vehicle injection (p< 0.05). Mean blood pressure levels in SHR receiving 10-propargyl-androst-4-ene,3,17-dione were lower than those in SHR receiving vehicle for each of the first 8 weeks of treatment (p< 0.05). These data support the importance of 10-nor-corticosteroids in the pathogenesis of hypertension in SHR.

ISSN:0194-911X    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Enzymatic dispersion and density gradient (Percoll) sedimentation were used to isolate a population of renin-containing, granule-laden cells (density 1.067 g/ml) from rat kidney cortex. Using immunohistochemistry (light microscopy) and electron microscopy, we defined the presence and ability of these cells to store renin protein(s). A 1000 base pair rat renin complementary DNA was used to show that these cells express the renin gene. The reverse hemolytic plaque assay defined the functional properties of the renin-containing cell. The data are consistent with the postulated inverse relationship between calcium concentration and release of renin. Thus, we have isolated a population of functional rat kidney cells that synthesize, store, and release renin.

ISSN:0194-911X    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Thrombin-induced aggregation and serotonin release were markedly enhanced in platelets from spontaneously hypertensive rats (SHR) when compared with those from normotensive Wistar-Kyoto rats (WKY). Since phosphoinositides are involved in calcium-mediated platelet responses, the metabolism of these lipids was investigated in SHR and WKY by using 32P-labeled quiescent platelets. In unstimulated cells, both the rate and extent of 32P incorporation into individual inositol-containing phospholipids and phosphatidic acid were identical in SHR and WKY. This finding suggests that the pool size and basal turnover of phosphoinositides did not differ between the two strains. In contrast, early thrombin-induced phosphoinositide metabolism, when monitored as changes in [32P]phosphatidic acid, was significantly higher in SHR than in WKY. For example, a 20-second exposure to thrombin, 0.3 U/ml, induced the formation of 1.6 times more [32P]phosphatidic acid in SHR than in WKY. These results provide evidence for a leftward shift of the dose-response and time-course curves of thrombin-induced [32P]phosphatidic acid formation in SHR. Moreover, the extent of the difference between SHR and WKY was independent of the extracellular calcium concentration. Following thrombin stimulation, [32P]phosphatidic acid formation likely reflects the initial agonist-receptor interaction; therefore, these results suggest that phospholipase C activity is enhanced in platelets of SHR and that the hypersensitivity of phospholipase C in SHR may play a role in the overall alteration of cell calcium handling and, hence, in the platelet responses of SHR.

ISSN:0194-911X    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Cerebral and renal α-adrenergic receptors play an important role in the control of blood pressure. We studied α-adrenergic receptors in the cerebral and renal cortex of Milan hypertensive strain (MHS) and normotensive strain (MNS) rats, a genetic model of spontaneous hypertension linked to a kidney abnormality. Binding of the selective α1-adrenergic antagonist [3H]prazosin and the α2-adrenergic antagonist [3H]rauwolscine was used for receptor studies in tissues of prehypertensive (24-day-old) and hypertensive (60-day-old) rats. In the cerebral cortex, no between-strain differences in α-adrenergic and α2-adrenergic receptor density and affinity were observed in prehypertensive and hypertensive periods. The density of these receptors increased similarly with age in MHS and MNS rats. In the renal cortex, the differences between MHS and MNS rats concerned α2-adrenergic receptors only. Compared with their age-matched normotensive controls, MHS rats showed 1) a lower affinity for the antagonist (p< 0.05) in the prehypertensive period, 2) absence of the normal agerelated increase in receptor density, and 3) a lower density of [3H]rauwolscine binding sites (p< 0.001) in the hypertensive period. In this period, studies of competitive inhibition of [3H]rauwolscine binding showed that 7-epinephrine bound to one class of sites in MHS rats (pseudo-Hill plot, 0.90) and to two classes in MNS rats (pseudo-Hill plot, 0.68). In addition, the lack of any guanylylimidodiphosphate effect on the 7-epinephrine competition curve observed in MHS rats suggests the uncoupling of these receptors from the guanosine 5′-triphosphate binding protein. The modifications of renal α2-adrenergic receptors were more evident in the hypertensive period when the impaired tubular sodium reabsorption observed in the prehypertensive period had almost returned to normal. Taken together, these data suggest that the modification of renal α2-adrenergic receptors in MHS rats could be a compensatory mechanism to counteract the increased renal sodium reabsorption rather than the cause of the development of hypertension in MHS rats.

ISSN:0194-911X    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

To determine if hypertension could be produced in normal rats by feeding them a fructose-enriched diet, Sprague-Dawley rats were fed either normal chow or a diet containing 66% fructose as a percentage of total calories for approximately 2 weeks. At the end of this period systolic blood pressure had increased from 124 ± 2 to 145 ± 2 (SEM) mm Hg in the fructose-fed rats, whereas no change occurred in the control group. In addition, hyperinsulinemia and hypertriglyceridemia were associated with hypertension in fructose-fed rats. The addition of clonidine to the drinking water inhibited fructose-induced hypertension, but not the increase in plasma insulin or triglyceride concentration seen in fructose-fed rats. Thus, the metabolic changes associated with fructose-induced hypertension are unlikely to be secondary to an increase in sympathetic activity. Whether or not this is also true of the hypertension remains to be clarified.

ISSN:0194-911X    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Although the existence of so-called streptozocin hypertension seems well established, some reports have indicated that no rise in blood pressure (BP) occurred after streptozocin treatments. To ascertain the streptozocin-induced BP response, normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were treated with streptozocin, 40 to 45 and 35 mg/kg i. v., respectively, and BP was determined directly and indirectly every week for 3 to 4 weeks. Direct mean BP was determined without anesthesia or restraint through a cannula inserted into the rat's abdominal aorta. Indirect BP was determined at the tail without anesthesia after prewarming the rat in a holder. Compared with control values, indirect BP increased significantly in diabetic WKY 2 weeks after streptozocin treatment. In contrast, direct BP of these rats decreased, compared with control values. Indirect BP of diabetic SHR was as high as that of the controls, whereas direct BP of diabetic SHR decreased significantly 1 week after the treatment and thereafter, compared with control values. These discrepancies between the direct and indirect BP values may be caused by severe emaciation of diabetic rats. Extra pressure in the cuff may be necessary to occlude the bloodstream. These results indicate that under these conditions the value of BP obtained by the direct measurement is more reliable than that by the indirect one; therefore, we concluded that so-called streptozocin hypertension does not exist.

ISSN:0194-911X    

出版商:OVID    

年代:1987

数据来源: OVID