摘要:

Release of arachidonic acid from membrane phospholipids is a limiting step in the synthesis of both cyclooxygenase products and lipoxygenase products. The direct effects of prostacyclin and some lipoxygenase products on renin release were studied using rat renal cortical slices. Prostacyclin, at concentrations of 10−5M, stimulated renin secretion, but this effect was short-lived. Leukotrienes or their precursor, 5-hydroperoxyeicosatetraenoic acid, did not affect basal renin release. In contrast, 10−9M 12-hydroperoxyeicosatetraenoic acid and 10−8M 12-hydroxyeicosatetraenoic acid were potent inhibitors of renin secretion. Similarly, 15-hydroperoxyeicosatetraenoic acid and its hydroxy derivative, 15-hydroxyeicosatetraenoic acid, at somewhat higher molar concentrations (10−6M) also reduced basal renin. These studies confirm prostacyclin as a potential renin secretagogue; however, its action in vitro is transient, probably because of its rapid degradation. Our studies provide new evidence that products of the 12-lipoxygenase and 15-lipoxygenase pathways, reported to be present in renal vascular tissue, are potent inhibitors of renin secretion and much more active on a molar basis on renin secretion than is prostacyclin. These studies suggest the potential presence of a dual system of stimulation and suppression that may regulate renin secretion in normal and clinical states.

ISSN:0194-911X    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

We studied the effect of 12 weeks of ethanol feeding on arterial blood pressure and baroreceptor reflex control of heart rate in Sprague-Dawley and Wistar rats. Baroreceptor reflex sensitivity and pressor responsiveness were evaluated by evoking graded rises in mean arterial pressure with increasing doses of phenylephrine and angiotensin II. After 12 weeks of ethanol feeding there was a modest increase in mean arterial pressure with no change in heart rate in both strains. When angiotensin II or phenylephrine was used as the pressor agent, baroreceptor reflex curves (relationships between changes in mean arterial pressure and heart rate) of Wistar rats were shifted upward and had a markedly reduced slope compared with those of control rats, suggesting that impairment of baroreceptor reflex control of heart rate had occurred. This effect was less evident in the Sprague-Dawley rats. Ethanol-fed rats had a higher sympathetic activity, since β-blockade with propranolol decreased heart rate to a greater degree than that seen in control rats. The pressor response curve of phenylephrine was shifted to the right in control rats challenged with ethanol (0.5 g/kg), implying the presence of α-blockade. This shift was not present in ethanol-fed rats, showing that tolerance had developed to this effect of ethanol. These findings show that attenuation of baroreceptor reflex function is associated with ethanol-induced hypertension but do not establish whether this is a cause or an effect of the developed hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Since various studies suggest that chronic physical conditioning promotes myocardial vascularity, we investigated whether it could prevent the coronary reserve abnormalities of hypertensive cardiac hypertrophy. One week after operation, female Sprague-Dawley rats with two-kidney, one clip Goldblatt hypertension were either subjected to a moderate exercise program by swimming (n = 21) or kept sedentary (n = 16) for 9 weeks. Sedentary (n = 16) and exercised (n = 15) shamoperated rats served as controls. Maximal coronary blood flow and minimal coronary resistance, either per unit mass or for the entire left ventricle, an index of the functional cross-sectional area of the coronary resistance vessels, were determined in conscious, unrestrained rats by left atrial microsphere injection following maximal vasodilation with carbochrome (12 mg/kg). Following exercise, left ventricular mass was moderately (+ 5–10%) but significantly increased in normotensive rats, whereas left ventricular hypertrophy was significantly accentuated in the hypertensive rats. Minimal coronary resistance for the entire left ventricle was significantly decreased (−24%) in normotensive rats but did not change significantly in hypertensive rats. Minimal coronary resistance per unit mass (the coronary vasodilator reserve) tended to decrease in normotensive rats (−17%), whereas it tended to be further augmented in hypertensive rats (+13%). However, these differences were marginally significant and were not associated with any changes in maximal coronary blood flow per unit mass (the coronary flow reserve). Thus, in normal rats, exercise promoted myocardial arterial vascularity in parallel with the development of cardiac hypertrophy. However, when superimposed on hypertensive hypertrophy, exercise did not stimulate vascular growth, and the limitation in coronary vasodilator reserve characteristic of hypertensive cardiac hypertrophy was not prevented.

ISSN:0194-911X    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The responses to alterations in extravascular pressure were studied in five orders of arterioles in the cheek pouch of normotensive and renal hypertensive hamsters. Renal hypertension was induced by bilateral compression of both kidneys using figure-of-eight ligatures. Ten to 16 days later, hamsters were anesthetized with pentobarbital (6.0 mg/100 g body weight) and a Plexiglas chamber was positioned in the cheek pouch. Chamber pressure, or extravascular pressure, was increased and decreased by ± 10, 20, and 40 mm Hg, and arteriolar diameters were monitored continuously. The responses at −20 mm Hg and the slope of the linear portion of the chamber pressure-diameter curve (arteriolar gains) were compared between groups for each branching order of arteriole. Arteriolar responses at one chamber pressure and the arteriolar gains were enhanced in third and fourth order arterioles of the renal hypertensive group compared with the normotensive group, and the responses of these small arterioles were greater than those of larger arterioles in both groups. Control diameters of second and third order arterioles were significantly smaller in the renal hypertensive group, while the diameters after adenosine were not different. These results suggest that the enhanced responses of small arterioles in the renal hypertensive group were hot related to structural alterations but may be related to an increased reactivity of smooth muscles in these small arterioles to volume expansion, thus a pressure stimulus.

ISSN:0194-911X    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Fatty acid binding protein was purified from renal medulla, and its binding activity and fatty acid composition were determined in spontaneously hypertensive stroke-prone rats (SHRSP). Wistar-Kyoto rats (WKY) were used as controls. Fatty acid binding activity was higher in 5-week-old prehypertensive SHRSP than in control WKY (0.155 ± 0.006 vs 0.030 ± 0.001 mol palmitic acid/mol protein). However, in 40-week-old rats, the activity was decreased only in SHRSP with established hypertension (0.035 ± 0.002 vs 0.028 ± 0.003 mol palmitic acid/mol protein WKY). Fatty acid compositions were similar among 5-week-old and 40-week-old control WKY and 5-week-old SHRSP (palmitic acid, 24%; stearic acid, 14%; oleic acid, 30%; linoleic acid, 29%; arachidonic acid, 3%), although the total amount of bound long-chain fatty acids was decreased in 5-week-old SHRSP, explaining the high fatty acid binding activity in this preparation. Fatty acid binding protein from 40-week-old SHRSP had an elevated proportion of endogenous arachidonic acid, with other fatty acids being relatively reduced (palmitic acid, 8%; stearic acid, 2%; oleic acid, 4%; linoleic acid, 10%; arachidonic acid, 76%), indicating increased arachidonic acid transport in the cytosol. These results show that genetically hypertensive rats had an alteration in fatty acid transport mediated by fatty acid binding protein; this alteration may be involved in the pathogenesis of hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Phospholipase C activity and diglyceride lipase activity were studied in the renal cortex and medulla of 10- and 40-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and agematched normotensive Wistar-Kyoto rats (WKY). Enhanced phospholipase C activity was found in the cortical and medullary cytosol of kidney from SHRSP, and microsomal diglyceride lipase in SHRSP also increased. In SHRSP, phospholipase C and diglyceride lipase activities increased with age, but this increase was not evident in WKY. Phospholipase C had high substrate specificity for phosphatidylinositol in renal cytosol of both WKY and SHRSP. The increased activities were accompanied by prostaglandin E2synthesis in renal medullary microsomes of 10-week-old SHRSP and were also present in the kidney of 40-week-old SHRSP. Total phospholipid and arachidonic acid contents in kidney were markedly high in the medulla of 10-week-old SHRSP, but these lipids were decreased in 40-week-old SHRSP. These results suggest that phospholipids and arachidonic acid in SHRSP may be genetically high and that the activated phospholipase C and diglyceride lipase hydrolyze phospholipids, providing arachidonic acid for prostaglandin synthesis, which results in a decrease of phospholipids and arachidonic acid in the kidney of 40-week-old SHRSP. These studies demonstrate that a phosphatidylinositol-specific phospholipase C-prostaglandin synthetic system may play an important role in the course of hypertension in SHRSP.

ISSN:0194-911X    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

There is evidence that atrial natriuretic factor (ANF) has an action in the inner medullary collecting duct. In addition, the prehypertensive Dahl salt-sensitive (S) rat has an intrinsic tendency toward less natriuresis than the Dahl salt-resistant (R) rat has when challenged with ANF. To test the hypothesis that renal papillary collecting tubule cells from prehypertensive S rats might be genetically less responsive to ANF, S and R cells were grown in culture and studied for responsiveness to ANF by measurement of cyclic nucleotide responses. There was a concentration-dependent effect of ANF on renal papillary collecting tubule cell synthesis of intracellular cyclic guanosine 3′,5′-monophosphate (cGMP) in both strains. However, the S cells were hyporesponsive compared with the R cells (p< 0.002, by analysis of variance). Likewise, in response to Na nitroprusside, the S cells were hyporesponsive compared with the R cells as measured by intracellular cGMP accumulation (p< 0.03, by analysis of variance). Arginine vasopressin stimulated intracellular cAMP equally in both strains. Also, ANF equally enhanced intracellular cGMP in glomerular mesangial cells from S and R rats, indicating possible specificity of the reduced responsiveness to ANF to the distal nephron of S rats. Plasma ANF levels had a slight tendency to be higher in prehypertensive S rats than in R rats (p = 0.088, by I test). These results suggest that the papillary collecting duct of Dahl S and R rats may differ in guanylate cyclase activity. This difference may partially explain the impaired natriuretic responses of S rats and could represent a factor contributing to the development of salt-sensitive hypertension.

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:

Nephrectomized rats have above-normal plasma prorenin levels, presumably of extrarenal origin, but essentially no renin, suggesting a lack of “convertase” for prorenin activation. Adrenalectomized rats have low plasma prorenin levels accompanied by high renin activity, suggesting enhanced prorenin activation by the action of a stimulated “convertase” mechanism. Crosscirculation between adrenalectomized and nephrectomized rats for 15 or 30 minutes, dramatically lowered prorenin and raised renin levels in both types of rats, suggesting extensive activation of prorenin to renin. Similarly, in vitro mixing of these bloods (without cross-circulation) raised renin activity over five times the expected calculated level, while prorenin essentially disappeared. In both cases, prorenin from nephrectomized rat plasma apparently was activated to renin by the enhanced action of “convertase” in the adrenalectomized rat plasma. This newly generated renin activity was, like normal plasma renin, almost completely inhibited by a monoclonal antibody against hog renin and generated an immunoreactive angiotensin I. In contrast, cross-circulation or in vitro mixing of blood from normal control and nephrectomized rats produced little detectable activation of prorenin and only modest increments of renin, suggesting relative inactivity of the “convertase” mechanism in normal plasma. Our data suggest that activation of plasma prorenin is a significant regulated pathway for renin production, as it is greatly stimulated after adrenalectomy and deficient after nephrectomy, thereby implicating the kidney as an important contributor to the “convertase” mechanism operating within the circulation.

ISSN:0194-911X    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The spontaneously hypertensive rat (SHR) initially bred in Kyoto is the most widely studied animal model of essential hypertension. As controls for the SHR, most workers have used normotensive descendants of Wistar rats from the colony in Kyoto from which the SHR strain was derived (Wistar-Kyoto rats, WKY). But the presumption that WKY are serviceable controls for SHR rests on the tacit assumption that all WKY constitute a single inbred strain. It appears, however, that whereas the National Institutes of Health distributed breeding stocks of SHR after they had been fully inbred (i.e., after 20 generations of brother-sister mating), the breeding stocks of WKY were distributed before they had been fully inbred. Accordingly, the biological variability of WKY may be greater than that of SHR. To investigate this possibility, we obtained SHR and WKY from two of the largest commercial suppliers in the United States and systematically measured the growth rate and blood pressure of these rats under identical physical and metabolic conditions. We found that WKY from one source differed from those of the other in both growth rate and blood pressure. In contrast, the SHR from the two suppliers were not different with respect to either growth rate or blood pressure. Because the National Institutes of Health may have distributed breeding stocks of WKY as early as the F6generation, it is possible that rats currently designated as WKY do not constitute a single inbred strain. Thus, interpretation of studies employing “the Wistar-Kyoto rat strain” as a control for the SHR may be much more problematic than has previously been recognized.

ISSN:0194-911X    

出版商:OVID    

年代:1987

数据来源: OVID