Renin-producing renal cell carcinomas—clinical and experimental investigations on a special form of renal hypertension

Summary The pathogenetic relationship between tumour and hypertension was investigated in 129 patients with renal cell carcinoma, of whom 41 (31.8%) were hypertensive. Of these 41 patients with renal tumours and hypertension, 6 (14.6%) were found to have primary reninism. In these patients the plasma renin activity in blood from the renal veins showed a tumour kidney to contralateral kidney ratio of between 4 and 7, and 2 patients also had secondary hyperaldosteronism. In the same 6 cases the renin content in the renal tumour tissue was significantly higher than that in tissue from the adjacent tumour-free renal cortex of the ipsilateral kidney. Immunohistochemical demonstration of renin in the tumour was only possible in these 6 cases. In 5 of these patients blood pressure returned to normal following nephrectomy; in the 6th case there was a drop in blood pressure after nephrectomy. In 3 renin-positive tumours examined, autonomous renin production was demonstrated in cell culture. Renin-producing renal cell carcinomas are an uncommon cause of renal hypertension. The differential diagnosis of hypertension should therefore also include renal tumour.     

全麻手术对肥胖患者血浆抵抗素和肾素血管紧张素及血糖的影响

目的　研究全麻诱导以及手术对肥胖患者血浆抵抗素 (resistin)和肾素、血管紧张素Ⅱ及血糖的影响。方法　选择 4 0例全麻手术患者 ,根据BMI指数分为两组 :A组 (BMI>2 5 ) 2 0例为肥胖者 ;B组 (2 1 相似文献   

Neuroendocrine aspects of the serotonergic hypothesis of depression

This review examines the role of serotonin (5-HT) in depression. Dysfunction of serotonergic neurons has been implicated as one of the causes of endogenous depression. Since serotonergic neurons innervate the hypothalamus and these neurons send collaterals to several other brain areas, it is possible that hypothalamic sites which control hormone secretion receive the same serotonergic afferents that innervate other limbic areas in the brain. Several investigators have devised neuroendocrine challenge tests measuring the effect of 5-HT agonists on plasma cortisol and prolactin in depressed patients. These tests help to identify dysfunctional 5-HT neurons, and are a "window into the brain." The secretion of cortisol and prolactin is increased predominantly by 5-HT1 receptors. However, changes in 5-HT2 receptors have also been implicated in depression. Results from our laboratory and by others suggest that brain serotonergic neurons stimulate renin and vasopressin secretion by activation of 5-HT2 receptors. Therefore, the renin and vasopressin response to 5-HT agonists should be included in neuroendocrine tests of serotonergic function in affective disorders. Since antidepressants produce a decrease in the density of 5-HT2 receptors, renin and vasopressin could be used to evaluate the antidepressant potential of new drugs.     

Hormone changes induced by 37.5-h head-down tilt (−6°) in humans

Endocrine regulation of hormones and electrolytes during 37.5 h of –6° head down tilt (HDT) was studied in 13 men. The acute effects of simulated weightlessness are today well documented, but no study has been made concerning the hormone changes between 12 h and 2 days of HDT. Plasma volume showed a maximal increase of 9.23 (SEM 1.97) % after 6.5 h (P<0.01) and had returned to prestudy levels after 13.5 h of HDT. From 1.5 h to 4 h of HDT, C-terminus and N-terminus atrial natriuretic peptide (ANP) concentrations in plasma were increased by about 50% (P<0.01) and thereafter declined to pre-HDT levels. Plasma renin activity (PRA) was decreased by 47% (P<0.05) after 4 h of HDT; PRA increased after 23.5 h to 60%; noradrenaline concentration decreased immediately and remained low up to 37.5 h. Diuresis and natriuresis were evident during the 1st day of HDT, resulting in a marked increase in the urinary Na⁺. These results showed that the initial hormone (ANP, PRA) changes during HDT did not last more than 13.5 h and that after 24 h a new state would seem to have been established to adapt the body to hypovolaemia.     

Renin,aldosterone and Cortisol during ethanol intoxication and hangover

The effect of ethanol intoxication and hangover on plasma renin activity (PRA), plasma aldosterone (PA) and plasma Cortisol (PC) concentrations was studied in 7 healthy supine men in controlled clinical conditions during 18 h beginning at 6 p.m. Large individual variation was observed in the response of PRA, PA and PC to ethanol. Following ethanol, stimulation of PRA was observed at the 14th and the 16th hour (P<0.05), of PA at the 4th and the 6th hour (P<0.01 and P<0.05, respectively) and of PC at the 4th and the 14th hour (P<0.01 andP<0.05, respectively). Ethanol ingestion suppressed PC during the first hour (P<0.02). Water ingestion at 8 a.m. suppressed PA between the 14th and the 16th hour (8–10 a.m.) in control and ethanol experiment (P<0.01 and P<0.005, respectively). There was a dissociation between PRA and PA, but intra-individually PRA and PA correlated fairly or well. Plasma arginine vasopressin (AVP) and PC were also significantly correlated. The results suggest that changes in PA and PC as well as the dissociation of PRA and PA after ethanol ingestion might be partly related to dehydration and to the increased secretion of hypothalamic and pituitary hormones as well as to sodium and potassium balance. There was a biphasic effect of ethanol, including an initial suppression of PC and a subsequent increase of PC, PRA and PA. Upright posture appears to exaggerate the stimulating effect of ethanol on PRA, PA and PC.     

Amiloride enhances the secretion but not the synthesis of renin in renal juxtaglomerular cells

In this study we have examined a potential role of the sodium/proton exchange system in the regulation of renin secretion. We found that the inhibitors of the Na⁺/H⁺ antiport, amiloride (1 mM) and ethylisopro-pylamiloride (EIPA, 50 M), led to a 125% increase of renin secretion from cultured mouse juxtaglomerular cells. The stimulatory effect of EIPA on renin secretion was dependent on the extracellular concentrations of sodium and hydrogen ions. While lowering the extracellular pH from 7.3 to 7.0, and lowering [Na⁺]_e from 130 mM to 5 mM had no effect on basal renin release, it markedly attenuated or even blunted the effect of EIPA on renin secretion. The stimulatory effect of forskolin on renin secretion, however, was not altered by decreases of extracellular pH and of sodium. Inhibition of basal renin release was achieved with angiotensin II (1 M). In the presence of EIPA the inhibitory effect angiotensin II was markedly attenuated. Although effective on renin secretion, neither amiloride nor EIPA exerted a significant effect on the de novo synthesis of renin in cultured mouse JG cells. These findings are compatible with the idea that an amiloride-sensitive transport process, presumably the Na⁺/H⁺ exchanger, acts indirectly as an inhibitory signal transduction system for renin secretion from renal juxtaglomerular cells.     

Calcitonin gene products and the kidney

Summary Calcitonin gene-related peptide (CGRP) is localized in capsaicin-sensitive nerve fibres in the kidney and urogenital tract whereas calcitonin reaches the kidney through the general circulation. Systemic infusion of CGRP and perfusion of isolated rat kidney reduces vascular resistance, and increases renal blood flow and glomerular filtration. CGRP stimulates renin secretion in vivo and in vitro and inhibits contraction of isolated rat mesangial cells by angiotensin II. Calcitonin does not affect vascular resistance, renal blood flow and glomerular filtration, and is less potent in stimulating renin secretion, and does not alter contraction of isolated rat mesangial cells by angiotensin II. CGRP also exerts renal tubular effects brought about probably through interaction with calcitonin receptors. To this end, increased excretion of sodium and chloride, and stimulation of urinary flow are less pronounced with CGRP than with calcitonin. Calcitonin, moreover, stimulates the fractional urinary excretion of calcium and phosphate.     

Age-related profile of cardiovascular reactivity to norepinephrine and angiotensin II in normal and hypertensive man

Summary The interrelationships among age, cardiovascular pressor reactivity to intravenously infused norepinephrine (NE) or angiotensin II, and endogenous plasma NE or renin (PRA) levels were evaluated in 31 normal subjects and 37 patients with essential hypertension. In normal subjects both angiotensin II pressor dose and PRA decreased progressively with aging. Angiotensin pressor dose correlated positively with PRA (r=0.41,P<0.025) and inversely with age (r=–0.46,P<0.02). NE pressor dose and basal plasma NE were also positively correlated (r=0.53,P<0.005), but the two factors remained largely unchanged with aging. Findings in essential hypertension differed in certain aspects. Angiotensin II pressor dose did not correlate with either basal PRA or age; and pressor doses of NE and angiotensin II tended to be lower in some patients than in normal subjects. These findings indicate that aging is accompanied by a physiologic increase in cardiovascular reactivity to angiotensin II, probably due to a concomitant decrease in circulating renin. The dissociation between angiotensin pressor dose and PRA in essential hypertension suggests an interference from an other factor.This work was supported by the Swiss National Science Foundation     

Captopril in Cushing's syndrome

Summary To analyse the role of the renin angiotensin system in the pathogenesis of hypertension in Cushing's syndrome ten patients with hypercorticism (five with pituitary hypothalamic dysfunction, three with adrenal adenomas and two with adrenal carcinomas) received a single oral dose of 25 mg captopril. Mean arterial pressure was then determined at short intervals over periods of up to 240 min. Plasma renin activity (PRA) was measured immediately before the administration of captopril. Eleven patients with severe essential hypertension, who showed a comparable distribution of basal PRA values, served as a control. Patients with elevated basal PRA values (>3 ng/ml·3 h) showed, both in the subgroup of cases with essential hypertension and in that with Cushing's syndrome, a statistically significant fall (P<0.05–P<0.001) in mean arterial pressure, the decrease being slightly more pronounced in essential hypertensives. On the other hand patients with normal PRA values (3 ng/ml·3 h) exhibited only a minor fall in mean arterial pressure reaching statistical significance (P<0.05) only after 60 min (essential hypertension) and 180 min (Cushing's syndrome), respectively. Our results document that in patients with Cushing's syndrome the effect of captopril seems to be determined by the activity of the renin angiotensin system. Thus, in a substantial number of patients with hypercorticism, the renin angiotensin system may be an important factor in the pathogenesis of hypertension, whereas in patients with low PRA values other factors like oversecretion of mineralocorticoids may be responsible for the observed blood pressure increases.     

Hepatische Extraktion und Clearance von Renin bei Lebercirrhosen

Zusammenfassung Bei 14 kompensierten und 8 dekompensierten Lebercirrhosen wurden Vergleichsbestimmungen der Renin-Aktivität (RA) im arteriellen und Lebervenenblut (Methode Kaneko et al.) durchgeführt. Die errechnete hepatische Renin-Extraktion (HE %) ist im Gegensatz zu Befunden anderer bei Cirrhosekranken nicht aufgehoben. Die Einzelwerte sind weit gestreut, die HE beträgt bei kompensierten Cirrhosen durchschnittlich 17,8±17,3%, bei dekompensierten Cirrhosen 30,5±5,8%. Ein signifikanter Unterschied der HE zu einer Vergleichsgruppe Hochdruckkranker (Mittelwert 28,5±20,4%,n=20) besteht nicht (p>0,05 bzw.>0,4).Aus den bei der Mehrzahl der Cirrhosekranken durchgeführten Bestimmungen leberhämodynamischer Größen geht hervor, daß die Renin-Extraktion der Tendenz nach mit dem Lebervenenverschlußdruck ansteigt (r=–0,393,p>0,05). Zum hepatischen Plasmafluß, bestimmt mit der Indocyaningrün-Methode, ergibt sich eine umgekehrte, statistisch allerdings nicht gesicherte Beziehung (r=–0,427,p>0,05). Es wird geschlossen, daß die hepatische Extraktion von Renin bei Lebercirrhosen vermutlich durch die intrahepatische Passagezeit beeinflußt wird.Unter Berücksichtigung der für die Vergleichsgruppe errechneten hepatischen Renin-Clearance (HRC) von 292±178 ml/min ist die HRC bei kompensierten Cirrhosen auf 68%, bei dekompensierten Cirrhosen auf 42,5% herabgesetzt. Im Rahmen der komplexen Regulationsstörung des Renin-Angiotensin-Systems bei fortgeschrittenen Lebercirrhosen dürften danach nicht allein Änderungen der renalen Sekretion, sondern außerdem eine Einschränkung der hepatischen Renin-Clearance für die Aufrechterhaltung einer erhöhten Plasma-Enzym-Aktivität von Bedeutung sein.