摘要:

SUMMARY1. This study examined (i) whether blood‐infused epidermal growth factor (EGF) can pass into urine; (ii) whether infused labelled EGF behaves like endogenous plasma immunoreactive EGF; and (iii) which parts of the human nephron show morphological evidence of EGF synthesis?2. We infused human [131I]‐EGF into a volunteer. After 6 min, only 66% of the plasma counts represented intact EGF. At the end of infusion, the T 1/2 of EGF was calculated to be 1.6 min. The tail of the curve lasted for at least another 2 h. The total excretion of the labelled EGF was 2.45% of the infused dose and was proportional to the urine volume.3. After a water load, the excretion of endogenous EGF was, on the contrary, inversely related to urine volume.4. Immunohistochemically, human kidneys were not stained by monoclonal anti‐EGF antibodies but showed positivein situhybridization for EGF mRNA in the nuclei of glomerular mesangial cells, distal convoluted tubules and collecting tubules.5. We conclude that human kidneys synthesize EGF and release it into urine. Plasma‐derived EGF constitutes under normal conditions only a small part of the urinary EGF. Contrasting volume‐dependency of the excretion of endogenous and [131I]‐EGF requires further study and cautions against extrapolating results obtained with labelled EGF to physiological

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00402.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARY1. The haemodynamic and metabolic effects of oral intake of ∼30 mg/kg per dayN‐nitro‐l‐arginine (NOLA) were examined in sham and adrenocorticotrophin (ACTH, 0.5 mg/kg per day) treated conscious Sprague‐Dawley rats (n= 33).2. NOLA administration produced an increase in systolic blood pressure of 24±6 mmHg (P<0.001), but did not alter food or water intake, urine volume or electrolyte excretion in rats not treated with ACTH.3. Compared with sham injection, ACTH‐treated rats demonstrated an increase in systolic blood pressure (water + sham, 3±1 mmHg; water + ACTH, 16±3 mmHg;P<0.001), loss of bodyweight, and increases in water intake and urine volume.4. The magnitude of the blood pressure rise in ACTH‐treated rats was greater in those receiving NOLA than in those drinking water only (water + ACTH, 16±3 mmHg; NOLA + ACTH, 37±3 mmHg;P<0.05). Metabolic changes were similar.5. Inhibition of nitric oxide is unlikely to be a major determinant of ACTH‐induced hypertension in the rat, since NOLA increased blood pressure whether or not ACTH was administered, indicating an additive effect of ACTH and

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00403.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARY1. To determine the possible role of an endothelin in the development of postischaemic microvascular incompetence, isolated buffer‐perfused rat hearts were perfused with endothelin‐3 (ET‐3) in phosphate buffer.2. ET‐3 produced a reduction in coronary flow rate, heart rate and arrhythmia. There was a marked reduction in the density of competent capillaries, and the myocytes showed vacuolation and mitochondrial damage in regions where microvascular incompetence was most severe.3. These results indicate that ET‐3 can substantially reduce microvascular perfusion in the heart and can also cause damage to th

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00404.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARY1. The changes in plasma levels of thromboxane‐B2(TXB2) and 6‐keto‐prostaglandin‐F1α(6‐keto‐PGF1α) were examined in rats given 5, 25, 50 or 100 μg/mL nicotine in drinking water for 10 days.2. The effect of nicotine on prostacyclin (PGI2) synthesis from endogenous arachidonic acid by cultured rabbit aortic smooth muscle cells was also studied.3. Plasma levels of TXB2were increased dose‐dependently by treatment for 10 days with nicotine.4. 6‐Keto‐PGF1αvalues were lowered dose‐dependently, both in the plasma of nicotine‐treated rats and in rabbit aortic smooth muscle cells incubated with the alkaloid.5. The results suggest that endogenous synthesis of thromboxane‐A2and PGI2, as reflected by TXB2and 6‐keto‐PGF1αlevels, respectively, is influenced by nicotine treatment. These findings may be related to cardiovascular diseases associated with cigarette smoking

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00405.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARY1. The renal and hypotensive effects of a new angiotensin‐converting enzyme (ACE) inhibitor, cilazapril, were evaluated in 18 one‐kidney, one‐clip Goldblatt hypertensive rats (1K1C), 10 one‐kidney normotensive rats (1K) and eight 1K1C rats with acute unclipping (1KU). Cilazapril was infused intravenously (25 μg/kg per min) into anaesthetized rats, and the arterial blood pressure (BP) and renal clearance of rats were measured.2. In 1K rats, cilazapril reduced BP from 123 ± 4 to 117 ± 4 mmHg (P<0.05), and produced diuresis, natriuresis and kaliuresis without significantly changing glomerular filtration rate (GFR).3. In 1K1C rats, cilazapril significantly reduced BP (from 157 ± 5 to 143 ± 6 mmHg;P<0.05), GFR (14.4 ± 6.7%), urine flow (27.1 ± 8.5%) and sodium excretion (39.4 ± 7.4%). Mechanically graded reductions of renal arterial pressure alone also produced parallel decreases in GFR and renal excretory function.4. In 1KU rats, removal of the renal arterial clip significantly decreased BP and increased renal function. Subsequent infusion of cilazapril further reduced BP and urinary excretions of sodium and water but did not significantly change GFR.5. These results suggest that the renal function of the 1K1C hypertensive model is pressure‐dependent, and that ACE inhibitor exerts a mild antihypertensive effect but causes a pressure associated reduction in renal function. Furthermore, the detrimental effect of ACE inhibitor on the residual kidney persists after acute surgical correctio

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00406.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARY1. The responses of angiotensin II (AII), AIII, aldosterone and plasma renin activity (PRA) to a single dose of captopril were investigated in hypertensive patients receiving long‐term (more than I year) captopril therapy (CT patients) and compared with those of non‐treated hypertensive patients (NT patients).2. Baseline levels of AII and aldosterone were significantly lower in CT patients than in NT patients. AM tended to be lower and PRA was slightly higher in CT than in NT patients, but these differences were not significant.3. A single administration of captopril (50 mg orally) significantly decreased plasma levels of AII, AIII and aldosterone as well as blood pressure in both CT and NT patients.4. These results demonstrate that chronically repeated administration of captopril to hypertensive patients effectively reduces the daily blood pressure and concomitantly the plasma AII level to acceptable levels in patients with no experience of ACE inhibit

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00407.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARY1. This study investigated the effect of atrial natriuretic peptide on renin release from the kidney. Thein vitrodirect effect was examined in the animal experiment using renal cortical slices of rat, and thein vivoeffect was observed in the human infusion study.2. In thein vitroexperiments, α‐human atrial natriuretic peptide (α‐hANP) ranging 10−9to 10−6mol/L did not change the basal renin release rate from the renal cortical slices (∼9% at 10−6mol/L, NS). Isoproterenol (10−6mol/L) increased renin release by 40% (P<0.001), whereas angiotensin II (10−6mol/L) suppressed it by 48% (P<0.001). However, α‐hANP did not affect the stimulative effect of isoproterenol or the inhibitory effect of angiotensin II.3. Also in the human study, infusion of 25 ng/kg per min α ‐hANP failed to change the plasma renin activity in normotensive subjects (–4%) or patients with essential hypertension (+5%), or even in patients with raised renin levels such as renovascular hypertension (+ 10%) or congestive heart failure (‐13%).4. These results put forth negative views on the direct involvement of atrial natriuretic peptide in renin release from th

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00408.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARY1. The role of prostanoids in experimental colitis with trinitrobenzene sulfonic acid (TNBS) in rats was investigated. The effects of cyclosporine A (CsA) on the development of experimental colitis were also examined.2. Five kinds of prostanoids were detected in rat colonic tissue by high performance liquid chromatography. These were 6‐keto‐prostaglandin (PG) F1α, PGF2α, PGE2, PGD2and thromboxane B2.3. In TNBS‐induced experimental colitis, all prostanoid concentrations except PGD2increased, although the time courses differed from each other.4. Medication with indomethacin markedly reduced prostanoid concentrations in TNBS‐induced colitis. However, indomethacin did not show any effect on damage scores.5. Cyclosporine A reduced damage scores 14 days after TNBS treatment, and the protective effects were observed, whereas CsA did not affect colonic tissue prostanoid concentrations.6. Prostanoids might be produced secondarily in the genesis of TNBS‐induced colitis, although they may attenuate the inflammatory response. It was also suggested that CsA was likely to have therapeutic effects on experimental colitis by inhibiting the immune reaction with TNBS, which induced the chronic i

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00409.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARY1. To clarify the metabolism of contractile and non‐contractile proteins of the ventricles during the development of right ventricular hypertrophy (RVH) and accompanying congestive heart failure (CHF) in response to a pressure overload, monocrotaline was injected subcutaneously into Sprague‐Dawley (SD) rats. Myosin isoenzymes (MIE) were analysed by pyrophosphate gel electrophoresis under non‐dissociating conditions. Acid‐soluble collagens were analysed by an improved, non‐interrupted sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS‐PAGE). Tissue collagen content was also measured after the estimation of hydroxyproline concentration in tissues.2. Monocrotaline induced RVH, but not left ventricular hypertrophy, at 2 weeks after the injection of monocrotaline, with severe RVH with CHF present at 4 weeks. In the right ventricles (RV) treated with monocrotaline, MIE shifted significantly from V1 to V3 at 2 weeks. The shift of MIE was more pronounced at 4 weeks. The proportion of type III collagen increased significantly compared with controls at 2 weeks. At 4 weeks, the proportion of types III and V collagens increased significantly compared with controls.3. In left ventricles (LV) treated with monocrotaline, a similar but less remarkable shift of MIE was observed without remodelling of collagen types at 2 and 4 weeks. The concentration of collagen in either the RV or LV treated with monocrotaline showed no significant changes at 2 and 4 weeks compared with controls.4. These results demonstrate a remodelling of the contractile and non‐contractile proteins during the development of RVH and accompanying CHF, and provide evidence for changes in protein metabolism of the counterpart of RV (i.e. the LV). These results may provide important insights into the pathophysiology of adaptive or non‐adaptive cardiac hypertrophy in response to a pr

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1992.tb00410.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY