ISSN:0263-6352    

出版商:OVID    

年代:1991

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We compared the distribution of DNA synthesis over the arterial tree of young normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) with marginally elevated blood pressure. Six-week-old male SHR and WKY rats were therefore infused with 5-bromo-2'-deoxyuridine (BrdUrd) for 2 days and the nuclear incorporation of the thymidine analogue in the media of various arteries was determined by immunohistochemistry. In WKY rats, 2.5% of the arterial smooth muscle nuclei in elastic, muscular and resistance arteries incorporated BrdUrd. In SHR, DNA synthesis was more marked in large arteries than in resistance arteries. It was in addition significantly larger in the aorta, superior mesenteric, renal and femoral arteries of the SHR than in those of the WKY rats. However, nuclear incorporation of BrdUrd in vivo did not differ between SHR and WKY rats in aortic endothelium, carotid arterial smooth muscle, nor in mesenteric or renal resistance arteries. Between 6 and 20 weeks of age, the number of nuclear profiles per media cross-section did not increase in large arteries of WKY rats and SHR. During this period of time, however, carotid artery and thoracic aorta weight and DNA content increased. SHR large arteries gained more DNA than those of WKY rats. These data indicate that DNA synthesis is uniformly distributed over the arterial system in young WKY rats and that DNA synthesis is elevated in the smooth muscle of large arteries of 6-week-old SHR but not in their resistance arteries.

ISSN:0263-6352    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

This paper describes the kinetics of the Na+-K+pump and the Na+-K+-CI-cotransport in sodium-loaded erythrocytes and of the Na+-K+- Cl-cotransport in erythrocyte inside-out vesicles (IOV) from Milan hypertensive (MHS) and normotensive (MNS) rats in order to evaluate the possible role of intracellular factor(s). In intact erythrocytes, no difference was detectable in the Na+-K+pump kinetics between the two strains while the apparent affinity (Km) of Na+-K+-Cl-cotransport for internal sodium was significantly greater and the maximal rate of sodium transport lower in MHS when compared with MNS rats. IOV, which are depleted of cytoskeleton, showed a bumetanide-sensitive potassium- and chloride-dependent sodium uptake. However, the erythrocyte differences in Na+-K+-CI-cotransport activity and the Kmbetween strains disappeared in IOV, suggesting that the altered sodium transport of MHS erythrocyte might be due to some intracellular factor or a membrane skeleton protein abnormality.

ISSN:0263-6352    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We studied the effect of insulin at concentrations of 0 to 50 mU/l and glucose at 0 to 20mmol/l on Li+-Na+countertransport in erythrocytes from normotensive human subjects. While insulin produced a dose-dependent decrease in the rate of Li+-Na+countertransport, from 0.272 mmol/l erythrocytes per h at zero insulin to 0.081 at a concentration of 50 mU/l (P<0.0001), alterations in ambient glucose concentration had no significant effect on the rate of countertransport. Physiological levels of insulin appear to reduce Li+-Na+countertransport in vitro by a mechanism which is not related to glucose concentration or transport.

ISSN:0263-6352    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We designed experiments to reveal the antihypertensive properties of cicletanine, a novel antihypertensive drug, in Dahl salt-sensitive (Dahl-S) rats. Cicletanine (39 mg/kg body weight per day for 6 weeks) ameliorated the development of hypertension in Dahl-S rats fed a high-salt (4% NaCI) diet. This blood pressure reduction was associated with a decrease in heart weight and vascular wall thickness. Moreover, urinary prostacyclin (PGI2) excretion was increased with cicletanine treatment, being inversely related to systolic blood pressure. Proteinuria and urinary excretion of n-acetyl-β-D-glucosaminidase were decreased and glomerular filtration rate was increased with this treatment. Morphological investigation revealed an improvement in glomerulosclerosis, renal tubular damage and intrarenal arterial injury in the salt-induced hypertensive rats. In contrast, trichloromethiazide, which decreased blood pressure to the same extent as cicletanine, lowered urinary PGI2excretion and generally did not ameliorate the deteriorated renal functions and morphological abnormalities. Thus, these data indicate that cicletanine ameliorates the development of hypertension in Dahl-S rats and protects the cardiovascular and renal systems against the injuries seen in the hypertension. The enhanced vasodepressor PGI2synthesis probably participates, to some extent, in these beneficial properties of long-term cicletanine treatment.

ISSN:0263-6352    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The possibility that prostaglandin H2is an endothelium-derived contracting factor (EDCF) was evaluated in rings of thoracic aorta of spontaneously hypertensive rats (SHR). When the aortic rings were contracted with norepinephrine (10-7mol/l) and treated with acetylcholine (10-5mol/l), a relaxant response with a peak after approximately 1 min and a contractile response with a peak after approximately 7min were observed. When these rings were pretreated with a thromboxane A2/prostaglandin H2receptor antagonist (ONO-3708), the later contractile response was clearly inhibited and only a sustained relaxant response was observed. This relaxant response was completely inhibited by pretreatment with an inhibitor of nitric oxide production (N-nitroarginine methylester; NNM). When aortic rings in the basal condition were treated with NNM and then with acetylcholine, a contractile response with a peak after 7 min was observed, but this reaction was completely inhibited by pretreatment with ONO-3708. The rate of 6-keto-prostaglandin F1α production showed a peak of 1.4 x 10-6mol/l per min per tissue, 2-4 min after administration of acetylcholine. With exogenous prostaglandin H2(5 x 10-7mol/l), a peak contraction was observed after approximately 4 min, the degree and pattern of which were similar to that induced by acetylcholine. Endogenous prostaglandin H2is considered to be produced by the aortic rings in an amount sufficient to induce vascular contraction within 30 s, and the pattern of this contraction induced by acetylcholine resembles that induced by exogenous prostaglandin H2. These findings most strongly suggest that prostaglandin H2is an EDCF. It is also suggested that, in the rat aorta treated by acetylcholine, the vascular tonus is regulated by two factors, i.e. EDCF (prostaglandin H2) and endothelium-derived relaxing factor (nitric oxide).

ISSN:0263-6352    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The role of ions and cell membrane function in the pathogenesis of benign and malignant hypertension was investigated in spontaneously hypertensive rats (SHR). Ten-week-old male SHR (n=50) and SHR treated with deoxycorticosterone acetate (DOCA; n=70) and 1% NaCI drinking water were studied weekly for 14 weeks. Malignant hypertension developed only in DOCA-salt SHR and was characterised by severe hypertension, failure to thrive and renal fibrinoid necrosis. Fourteen DOCA-salt SHR and one SHR died. Extracellular (serum) and intracellular (erythrocyte and muscle) Na+, K+, Mg2+, Ca2+and muscle membrane Na+,K+-adenosine triphosphatase (ATPase), Ca2+-ATPase and Mg2+-ATPase were measured at various stages in the development of malignant hypertension. Three developmental phases were defined: benign, premalignant and malignant. DOCA-salt SHR showed persistent hypokalaemia. In the benign phase, there were no differences in Na+, Mg2+and Ca2+between SHR and DOCA-salt SHR. In the premalignant phase, serum and erythrocyte Mg2+and ATPase activity were significantly lower in DOCA-salt SHR compared with SHR. During the late premalignant and malignant phases, intracellular Ca2+and Na+were significantly higher in the DOCA-salt SHR compared with SHR. In view of these findings, the abnormalities in DOCA-salt SHR during the early phases of blood pressure elevation could be contributory factors to the development of malignant hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Increasing evidence suggests an association between hypertension and abnormalities of glucose metabolism. Since components of the renin-angiotensin system exist in a variety of tissues consistent with paracrine actions of the peptide, we sought to determine whether the pancreas contains a local angiotensin system. We report the presence of angiotensinogen messenger (m) RNA, angiotensinogen protein, angiotensin II and high-affinity binding sites for angiotensin II in the canine pancreas. These novel findings establish a foundation for future studies to evaluate whether angiotensin acts as a paracrine regulator of endocrine and/or exocrine functions of the pancreas.

ISSN:0263-6352    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Platelet activating factor (PAF) is produced by the rat renal papilla from a neutral lipid, alkylacetylglycerol. Renal release of another neutral lipid, antihypertensive neutral renomedullary lipid, and PAF might account for normalization of blood pressure after unclipping in Goldblatt hypertensive rats. We studied the potential storage and release of hypotensive substances by the rat renal papilla in vitro. Rat kidneys were snap-frozen in liquid N2-cooled freon immediately after removal and the total lipids were extracted from pooled dissected papillae and partially separated by thin layer chromatography on silica gel with a hexane: ether: acetic acid (40:60:1) solvent system. Lipids eluted from four, contiguous silica gel zones were assayed in anesthetized spontaneously hypertensive rats. No hypotensive activity was found in the thin layer chromatography lipid fraction co-migrating with palmitylacetylglycerol or in any other neutral lipid fraction. In contrast, the Krebs medium obtained after 30-min incubation of freshly minced papillary tissue induced dose-related hypotension and bradycardia. The hypotensive activity was equivalent to 48 ± 9 ng prostaglandin E2(PGE2)/mg wet papilla. Bradycardia induced by the incubation medium was correlated with decrements in blood pressure. In the same assays, nitroprusside caused tachycardia which was correlated with hypotension, and the bradycardia associated with PGE2-induced hypotension was significantly less than that induced by the incubation medium. The dose-related effects of the incubation medium were dramatically attenuated by indomethacin treatment of the papilla, suggesting that the hypotensive activity is dependent upon papillary cyclooxygenase activity. However, PGI2elicited hypotension concomitant with tachycardia rather than bradycardia and PGE2did not mimic the incubation medium-induced bradycardia. Therefore, the effects of the papillary incubation medium may be mediated by other cyclooxygenase metabolites. Production/release of hypotensive material by indomethacin-treated papillary tissue was potentiated by co-incubation with non-hypotensive quantities of PGE2, suggesting a potential role for PGE2in the renal antihypertensive function. Increasing pressure on the papilla from 6 to 20mmHg during incubation did not increase release of non-prostanoid hypotensive substance(s). These results suggest that the formation and release of cyclooxygenase metabolites accounts primarily for the hypotensive activity released from rat renal papillae in vitro, and that prostaglandins might play a permissive role in the release of other renomedullary hypotensive substances.

ISSN:0263-6352    

出版商:OVID    

年代:1991

数据来源: OVID