ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Objective: In this study we determined whether the enhanced production of nerve growth factor (NGF) and the associated hypernoradrenergic innervation of the vasculature of the spontaneously hypertensive rat (SHR) was associated with an increased gene expression of messenger (m)RNA encoding for nerve growth factor.Design: It has been shown previously that the hypernoradrenergic innervation of the SHR occurs early, as does the enhanced expression for NGF. In this study we analysed the content of NGF mRNA in blood vessels from young SHR and normotensive Wistar-Kyoto (WKY) rats.Methods: Total RNA was isolated from mesenteric arteries from 2–, 10– and 43-day-old SHR and WKY rats and RNA was also isolated from caudal arteries from 43-day-old rats. The RNA was subjected to Northern transfer or slot blots and the content of NGF mRNA measured after hybridization with a32P-labelled complementary (c)DNA probe for NGF.Results: Slot blot analysis indicated a larger concentration of NGF mRNA in mesenteric and caudal arteries from SHR than for tissues from WKY rats.Conclusions: In this genetic model of hypertension the results indicate an association between an enhanced level of NGF mRNA and the appearance of vascular hypernoradrenergic hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Ojective: To test the hypothesis that effects of angiotensin converting enzyme (ACE) inhibitors upon resistance vessel structure are responsible for their ability to cause long-term reduction in blood pressure.Design: Stroke-prone spontaneously hypertensive (SHRSP) and Wistar-Kyoto (WKY) rats were treated with enalapril or hydralazine from 4 to 15 weeks of age. Effects upon tail-cuff blood pressure, left ventricular hypertrophy and structural indices of the superior mesenteric artery (SMA) and its resistance vessels were assessed at 11 weeks of treatment and up to 11 weeks post-treatment.Methods: Left ventricular hypertrophy was assessed by left ventricular weight: body weight ratios. Evidence of vascular structural change was obtained from tissue weight: body weight ratios, levels of RNA, DNA and expression of α-actin and elastin messenger (m)RNA.Results: The effects of enalapril and hydralazine upon left ventricular hypertrophy in SHRSP were consistent with their respective effects upon blood pressure. Both drugs prevented the development of medial hypertrophy in SMA and resistance vessels. This was accompanied by substantial reductions in RNA: DNA ratios. Alpha-actin mRNA levels were not affected by either drug but elastin mRNA levels were reduced by both drugs. During the first 12 days post-treatment there was evidence of structural change in SMA accompanying the increases in blood pressure but importantly not in the resistance vessels.Conclusion: The effects of enalapril upon left ventricular hypertrophy and mesenteric arterial hypertrophy are totally consistent with responses to blood pressure and the persistence of structural changes post-treatment does not underlie the ability of the ACE inhibitors to persistantly suppress hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Objective: To determinein vivowhether in young spontaneously hypertensive rats (SHR) dietary sodium restriction decreases adrenergic transmitter release from the sympathetic nerve terminal.Design: Dietary sodium restriction was initiated in young and mature SHR and Wistar-Kyoto (WKY) rats, and subsequently changes in pressor responsiveness to norepinephrine and to the indirectly acting sympathomimetic tyramine were determined in relation to their effects upon plasma catecholamines.Results: In young SHR sodium restriction for 3–6 weeks prevented the development of hypertension, whereas in mature SHR sodium restriction did not affect blood pressure. Sodium restriction caused modest decreases in pressor responsiveness to the exogenous α-agonist, not different in young and mature SHR compared with WKY rats. In contrast, sodium restriction markedly inhibited pressor responses to tyramine in young SHR and WKY rats, but not at all in mature rats. Tyramine increased plasma norepinephrine 5–10-fold. However, sodium restriction did not affect this response. The pressor response to tyramine was related to increases in total peripheral resistance, with minimal changes in cardiac output, and could be blocked by α1-receptor blockade in rats on either control or low-sodium diets.Conclusions: These results show that sodium restriction causes only a small decrease in the pressor response to norepinephrine, but a more marked inhibition of the pressor response to tyramine in young SHR and WKY rats without affecting the plasma norepinephrine response to tyramine. These results suggest that dietary sodium can indeed affect presynaptic functionsin vivo, but that plasma norepinephrine responses to tyramine may not reflect changes in arterial norepinephrine release, or that sodium restriction affects a co-transmitter rather than norepinephrine releaseper se.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Objective: To evaluate the cardiovascular effects of 1,25-dihydroxyvitamin D3(1,25-D).Design: Recent studies suggest that Ca-regulating hormones may contribute to the genesis of hypertension. We determined systemic and regional hemodynamics 24 h after administration of 1,25-D or vehicle to normal conscious Sprague-Dawley rats. In addition, to dissociate the vascular effects of 1,25-D from changes in serum ionized Ca2+, 1,25-D and vehicle were administered to rats maintained for 3 days on a low-Ca diet. To evaluate the effect of the slight rise in serum ionized Ca2+with 1,25-D administration, we infused CaCI or vehicle over 1 h into normal rats to raise the serum Ca2+to near that of rats treated with 1,25-D.Methods: The radioactive microsphere technique was used.Results: Systemic hemodynamics (blood pressure, heart rate, cardiac output, total peripheral resistance and stroke volume) did not differ between the two groups receiving a normal-Ca diet. In these rats 1,25-D significantly decreased renal blood flow (RBF), increased renal vascular resistance (RVR) and slightly increased serum ionized Ca2+. Similarly, in rats receiving a low-Ca diet, 1,25-D administration decreased renal blood flow, increased renal vascular resistance and caused only a minimal increase in serum ionized Ca2+. A low-Ca diet also increased heart rate, cardiac blood flow and renal blood flow. Although CaCI infusion raised serum ionized Ca2+, blood pressure, renal blood flow and renal vascular resistance did not change significantly.Conclusion: 1,25-D may constrict the renal vasculature directly or indirectly by enhancing the vascular sensitivity to circulating vasoconstrictors.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Objective: To study the effects of blockade of the renin—angiotensin system upon the development of hypertension, end-organ damage and mortality in Dahl salt-sensitive (DSS) rats using an angiotensin II receptor antagonist, losartan.Design and methods: DSS rats (n = 186) were fed 8% NaCI from 6 to 16 weeks of age. One group received losartan whilst the control group was untreated. Changes in blood pressure and plasma renin activity (PRA), as well as renal and cerebrovascular damage and survival were assessed during the study.Results: Losartan blunted the blood pressure rise only transiently. Salt loading suppressed PRA in both groups until week 4 and thereafter it rose more markedly in the treated group. With no treatment renal lesions were first detected at 2 weeks, and strokes at 6 weeks. However, losartan transiently decreased the incidence and delayed the progression of renal damage and cerebrovascular lesions (strokes) and increased survival. PRA correlated with renal damage and the incidence of strokes in both groups. Blood pressure only partially affected survival, but did not correlate with stroke incidence.Conclusions: These results indicate that whereas the rise in blood pressure is dependent upon sodium loading, morbidity and mortality in salt-loaded DSS rats are associated with activation of the renin-angiotensin system and are only partially related to blood pressure.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Objectives: The aim was to demonstrate whether prorenin is present in plasma from 24-h nephrectomized rats. Its existence and concentration is currently under debate.Design: Determination of the 50% inhibition concentration (IC50) values for inhibition of plasma renin in intact and 24-h nephrectomized rats. The potent and specific rat renin inhibitor CH-732 was used.Methods: Our previously published method for the determination of rat prorenin was used. It is characterized by removal of an interfering trypsin-formed angiotensin I immunoreactive material before the renin incubation step.Results: The trypsin-activated prorenin-like activity of 24-h nephrectomized plasma was due only to a minor degree to real prorenin as judged by CH-732 inhibition. The major part of the prorenin-like activity was due to a hitherto unknown sulphydryl enzyme, which could be blocked by N-ethylmaleimide. In normal plasma all prorenin was real prorenin. The plasma concentration of real prorenin in 24-h nephrectomized rats was approximately 10% of that in intact rats.Conclusion: Prorenin is definitely present in nephrectomized plasma, but in low concentrations. The data support the concept that the major part of plasma prorenin in intact rats originates from the kidneys. The previously published values for prorenin in intact rats were correct, whereas those in 24-h nephrectomized rats were too high. If N-ethylmaleimide is added to our previously published method for rat prorenin, it overcomes the three known problems with prorenin determination in rat plasma: trypsin generation of angiotensin I immunoreactive material; trypsin destruction of angiotensinogen; and interference in trypsin-activated nephrectomized plasma of a sulphydryl enzyme, which generates an angiotensin-I-like material.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Objective: To test the hypothesis that the secretion of medullipin I by the kidney involves an oxidative step.Design: Medullipin I is secreted by kidney renomedullary interstitial cells and is converted to medullipin II by the liver. Medullipin I can be derived from the kidney in the renal venous effluent by perfusing normal rat kidneys with 95% O2--5% CO2at an elevated pressure (180 mmHg). To evaluate whether the secretion of medullipin I involves an oxidative step normal rat kidneys were perfused at an elevated pressure in the presence of O2, in the absence of O2and after treatment of the kidneys with a powerful antioxidant.Methods: Normal rat kidneys were perfused with 5% albumin bubbled with O2-CO2at 180 mm Hg. This was the control procedure for each of the three approaches. In approach (1), the kidneys were perfused with 5% albumin bubbled with N2. In approach (2), the kidneys were perfused with 'blood' treated with carbon monoxide. In approach (3), the kidneys were treated with the antioxidant butylated hydroxytoluene then perfused with 5% albumin bubbled with O2-CO2. Each perfusate was tested for medullin I activity by rapid intravenous injection into the SHR.Results: All three approaches, which exclude the action of molecular O2, prevented the secretion of medullin I by the kidneys.Conclusion: The secretion of medullin I by the kidneys involves an oxidative step.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Objectives: To gain insight into the pathogenesis of hypertension in the spontaneously hypertensive rat (SHR), we compared the maturation of the Na-independent H+efflux and Na+-H+exchange in microdissected superficial proximal cortical tubule (PCD S1 and S2 segments of SHR and normotensive Wistar-Kyoto (WKY) rats.Methods: Isolated superfused PCT segments were loaded with 2'-7'-bis-carboxyethyl-5(6)-carboxyfluorescein and incubated in nominally HCO3-free solution. We assessed Na-independent N-ethylmaleimide (NEM)-sensitive H+efflux and Na-dependent H+efflux by measuring the recovery rate of the intracellular pH following acid loading induced by prepulsing with NH4+.Results: In young prehypertensive SHR the Na+-H+exchange recovery rate in S1 at pHi6.8 was significantly higher than in young WKY rats, whereas in adult rats no significant difference between the two strains could be observed. In S2 segments the Na+-H+exchange recovery rate was similar between SHR and WKY rats for both age groups. In the young, no difference in the NEM-sensitive H+efflux in S2 PCT was observed between the two strains. In contrast, in the adult, although the NEM-sensitive H+efflux had increased profoundly with age for WKY rats, it remained markedly low in SHR.Conclusions: These studies indicate that apical Na+reabsorption coupled with H+efflux in the S1 segment is increased in the PCT of SHR, and demonstrate a marked impairment in the maturation of H+pump activity in the S2 segment of the SHR compared with the normotensive strain. The impairment of these cell transport systems in the SHR may be relevant to the pathogenesis or maintenance of hypertension in this model.

ISSN:0263-6352    

出版商:OVID    

年代:1992

数据来源: OVID