[Endocrine function of the kidney].
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Erythropoietin↗
Biomedical subjects
F Fyhrquist
Publications and source records attributed to F Fyhrquist.
Renin-aldosterone axis in ethanol intoxication: effect of an ADH analogue (desaminocys1-D-arg8-vasopressin, DDAVP).
Plasma renin activity (PRA) is stimulated and renin-aldosterone nexus is broken in acute ethanol intoxication. Serial changes in renin-aldosterone axis were studied in five healthy males during moderate ethanol intoxication, while alcohol diuresis was prevented by 20 micrograms of an antidiuretic hormone analogue, desaminocys1-D-arg8-vasopressin (DDAVP), administered intranasally. The experiment was performed with the subject supine, and the amount of ethanol taken p.o., at a steady rate in 90 min, was 1.2 g/kg body weight, diluted with juice to 20 vol% solution. DDAVP prevented the stimulation of PRA, suggesting that dehydration due to alcohol diuresis is the main reason for this phenomenon during ethanol intoxication. However, there still was a dissociation between PRA and aldosterone, which may be caused by increased serum Na+/K+ ratio or an inhibitory action of ethanol on aldosterone secretion.
Adult↗
Comparison of sustained-release and standard preparations of clonidine in essential hypertension.
The antihypertensive drug, clonidine, was administered to 18 patients, 8 females and 10 males, with WHO grade I-II essential hypertension in two forms, either as sustained-release depot capsule of 250 micrograms once daily or as standard clonidine preparation, 150 micrograms twice daily. The two drug forms were administered for 2 months each, in a double-blind, crossover outpatient study. Both preparations were equally effective in reducing blood pressure. The depot form of clonidine was preferred by the patients because of fewer side effects, which included sedation and dry mouth. The antihypertensive effect of clonidine was unrelated to pretreatment plasma renin activity. Depot forms of clonidine appear to offer the advantages of once-daily dosing and fewer side effects than standard clonidine preparations.
Adult↗
Induction of angiotensin-converting enzyme with the ACE inhibitory compound MK-421 in rat lung.
Having observed that treatment of rats with captopril led to an increased ACE activity in serum and ACE concentration in lungs, we treated female Wistar Kyoto rats for 7 days with the esterified ACE inhibitor, MK-421 (1.0 mg/kg body weight per day), administered by Alzet osmotic minipump. Serum ACE activity decreased by 67% during MK-421 treatment when measured in non-dialyzed serum samples. Removal of the drug by dialysis unmasked a 280% increase of serum ACE activity. ACE concentration of crude lung homogenate increased 134% in MK-421-treated rats and ACE concentration in purified pulmonary plasma membranes increased by 34%. The increase of serum and lung ACE in MK-421-treated rats was similar to that seen in rats treated with captopril, and was probably due to induction of ACE biosynthesis. The mechanisms of this induction are unknown.
Angiotensin-Converting Enzyme Inhibitors↗
Induction of angiotensin I-converting enzyme in rat lung with captopril: the effect of adrenalectomy.
In spontaneously hypertensive rats, treatment with captopril, 0.2 g/liter of drinking fluid for 12 to 24 weeks, caused a threefold increase in serum angiotensin I-converting enzyme activity. Angiotensin I-converting enzyme increased 25 to 120 percent in lung plasma membranes. The elution profile of angiotensin I-converting enzyme on DEAE cellulose and after gel filtration on Sepharose 4B was unchanged by captopril. The Km value value also remained unchanged. In Wistar rats subjected to bilateral adrenalectomy, treatment with the same dose of captopril for 3 days resulted in increased serum angiotensin I-converting enzyme activity in both sham-operated and adrenalectomized rats, but angiotensin I-converting enzyme concentration increased in lung plasma membranes from sham-operated rats and captopril-treated rats only. We conclude that captopril causes induction of angiotensin-converting enzyme biosynthesis in spontaneously hypertensive and Wistar rats. The change is a quantitative one. Intact adrenal glands may be important for the incorporation of angiotensin I-converting enzyme into lung membranes.
Adrenal Glands↗
Effects of water deprivation and hyperhydration in pregnant and lactating goats.
The response to 30 h water deprivation was studied in 7 goats during the last month of pregnancy and during lactation with anestrus as the control period. Plasma osmolality and plasma Na concentration increased by about 4% in pregnant and lactating goats and by about 2% in anestral goats. Plasma AVP concentration rose by about 7 pg/ml in pregnant and lactating goats, but only by about 3 pg/ml during anestrus. PRA was elevated in pregnant animals, but dehydration caused only a minor further rise. Total plasma protein concentration was low in pregnant goats and did not increase during water deprivation, but it did so in lactating animals. Neither the hematocrit nor the plasma K concentration changed in response to dehydration. GFR fell by about 24% in pregnant goats and by 22% in lactating animals, but remained unchanged during anestrus. ERPF fell by 20% in lactating animals, but no consistent effect of the dehydration was seen during pregnancy and anestrus. Urine flow decreased by about 75% during pregnancy, 55% during lactation and 65% during anestrus with the highest urine osmolality observed during anestrus. Milk production was only slightly reduced, but the milk osmolality increased in parallel with that of the blood plasma. When allowed to drink at the end of the water deprivation period, pregnant goats immediately drank 2.5 +/- 0.5 litres, lactating goats 3.3 +/- 0.9 litres and anestral goats 1.1 +/- 0.3 litres. When hyperhydrated, pregnant goats excreted the excessive water more readily and showed less response to exogenous AVP than lactating and anestral animals. In conclusion, pregnant and lactating goats are obviously more susceptible to a shortage of water supply than anestral animals but can easily excrete an excess of water.
Animals↗
Effects of hemorrhage on vasopressin secretion and arterial blood pressure during experimental diabetes insipidus in goats.
The effect of hypotensive hemorrhage on plasma vasopressin (AVP) concentration and carotid blood pressure before and after induction of experimental diabetes insipidus (DI) was studied in the conscious goat. Bleeding to the point of blood pressure fall (blood loss 15-25% of the estimated blood volume) caused an immediate, approximately hundred fold, increase in the plasma AVP concentration in the normal animal. Hemorrhage to the same extent during DI did not affect the plasma AVP levels. A rather transient hypotensive response to bleeding was seen before disruption of the pituitary stalk, but during DI the recovery of the hemorrhage-induced hypotension was less effective. However, the normalization of the blood pressure after bleeding was slightly more efficient during the permanent than during the temporary phase of DI. It is concluded that an intact hypothalamo-neurohypophysial connection is necessary for the massive release of AVP normally seen in response to hypotensive hemorrhage. It is also confirmed that the lack of this hormonal response to bleeding is accompanied by an increased susceptibility to the hypotensive effect of hemorrhage.
Animals↗
Induction of angiotensin I-converting enzyme by captopril in cultured human endothelial cells.
Captopril (2.0 microgram/ml) increased angiotensin-converting enzyme (ACE, kininase II) activity from 6- to 16-fold in culture medium of human endothelial cells from umbilical cord artery. Immunohistochemically detectable ACE was markedly increased in these cells when using rabbit antihuman lung ACE antiserum. This accords with either observations of increased ACE activity in serum and lungs from rats treated with captopril and shows induction of ACE biosynthesis in human vascular endothelial cells in culture. This observation offers a tool for studying the mechanism of ACE induction.
Captopril↗
Bilateral oophorectomy and plasma renin substrate concentration.
Plasma renin substrate concentration was studied in 11 premenopausal women subjected to bilateral oophorectomy and hysterectomy. Preoperative plasma renin substrate concentration was 1573 +/- 477 ng angiotensin I/ml (mean +/- SD). Plasma renin substrate concentration did not change significantly after operation (1632 +/- 459 ng angiotensin I/ml) or after 3 months of postoperative estradiol valerate treatment (2 mg/day) (1762 +2- 467 ng angiotensin I/ml). It is concluded that non-pregnant levels of endogenous estrogens are of no significance in the regulation of plasma renin substrate.
Angiotensinogen↗
[Captopril-a new principle in the treatment of hypertension].
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Adult↗
Renin-aldosterone axis in ethanol intoxication.
The effect of acute moderate ethanol intoxication on renin-aldosterone axis was studied in four healthy humans in normal sodium and water balance. The subjects drank ethanol 1.2 g/kg body weight during 90 minutes. A dissociation between plasma renin activity (PRA) and plasma aldosterone took place; PRA increased (p less than 0.001) and aldosterone showed a decreasing trend, which was not significant. Serum Na+/K+-ratio increased (p less than 0.001). We observed no significant change in serum osmolality, blood pressure nor heart rate. The increase (p less than 0.001). We observed no significant change in serum osmolality, blood pressure nor heart rate. The increase in PRA was probably caused primarily by dehydration due to ethanol diuresis. The dissociation between plasma aldosterone and PRA may be associated with increasing serum Na+/K+-ratio or an inhibitory action of ethanol on aldosterone secretion.
Adult↗
Varying course of hypertension following renal trauma.
Hypertension developed in 5 patients after unilateral renal injury. The time-lag from injury to development of hypertension varied from 6 weeks to more than 3 years. In 2 of 3 patients with partial renal injury blood pressure normalized spontaneously. In the third patient sustained hypertension was cured by nephrectomy 56 months after injury. Nephrectomy led to normotension in the 2 patients with renal artery thrombosis, in 1 of them 14 years after renal trauma. Activation of the renin aldosterone axis was observed in all patients. The causes of varying time-lag from renal injury to onset of hypertension are obscure. Because of possible spontaneous regression of hypertension sufficient followup is recommended in patients with a history of renal injury. On the other hand, nephrectomy may be curative even after long-standing hypertension caused by traumatic renal artery thrombosis.
Adolescent↗
Aggravation of hypertension in spontaneously hypertensive rats by Heymann nephritis.
1. To explore the effect of nephritis on development of genetic hypertension we immunized 10-week-old spontaneously hypertensive rats with purified rat kidney brush-border antigen. This induces Heymann nephritis (autologous immune complex nephritis), which does not elevate blood pressure in normal rats. 2. Nephritis developed in 11 of the 12 immunized animals, and systolic blood pressure rose to a significantly higher level than in the non-immunized spontaneously hypertensive rats within 4 weeks. Blood pressure remained higher in the immunized rats at 17 weeks, heart weights were greater, but creatinine clearance remained unchanged. 3. At 6 weeks, urinary sodium excretion was greater in the immunized spontaneously hypertensive rats, whereas at 17 weeks, sodium excretion was decreased in these animals along with reduced serum protein concentration, packed cell volume and plasma renin activity, as compared with that of the controls. 4. Development of hypertension in nephritic rats, therefore, appeared unrelated to sodium excretion; signs of volume expansion emerged later. 5. Acceleration of the development of spontaneous hypertension by Heymann nephritis, also leading to sustained higher blood pressure levels than in spontaneously hypertensive rats, offers a new approach to experimental study of immune mechanisms behind acceleration of pre-existing hypertension. This may have important bearings on essential hypertension as well.
Animals↗
Dissociation of the effect of captopril on blood pressure and angiotensin converting enzyme in serum and lungs of spontaneously hypertensive rats.
Spontaneously hypertensive rats (SHR) of the Okamoto-Aoki strain (n = 40) were treated with captopril (SQ 14,225; D-3-mercapto-2-methylpropanoyl-L-proline) orally, dose 0.2 mg/ml in drinking water. The treatment was initiated early and later during the course of developing hypertension. Continuously treated rats did not develop hypertension. Rats receiving captopril for 12 weeks remained normotensive, whereas withdrawal of the drug resulted in hypertension. Captopril treatment was effective in the rats with established hypertension and decreased the blood pressures to nearly normal values. Serum angiotensin converting enzyme (ACE) activity rose 3-fold in captopril treated rats. ACE in lung plasma membranes increased during captopril treatment, indicating that captopril induced biosynthesis of pulmonary ACE. No qualitative differences were found in the ACE from treated and not treated animals. The dissociation of the antihypertensive effect of captopril and of increased ACE activity in serum and lungs reduce the value of relating blood pressure effects of the drug to measured enzyme activity in the SHR.
Animals↗
Plasma vasopressin concentration and renin in the rat: effect of hydration and hemorrhage.
In order to investigate effects of hydration state, different techniques of collecting blood samples, and of acute, stepwise hemorrhage, we studied plasma vasopressin (AVP) concentration, and plasma renin activity (PRA) in 80 female Wistar rats. Plasma AVP was decreased following hydration with 10 ml of water (1.0 +/- 0.3 pg/ml, mean +/- S.E.M.) as compared to controls (6.1 +/- 2.0 pg/ml), while withdrawal of water for 48 hours stimulated AVP release (29 +/- 8 pg/ml). AVP values in jugular venous blood during light ether anesthesia (9.6 +/- 4 pg/ml) were slightly higher than in trunk blood following decapitation (2.7 +/- 0.7 pg/ml). There was no effect of sham gastric lavage on AVP. PRA was slightly increased in trunk blood and in jugular venous blood following ether anesthesia, and 5-fold increased following 48 h of water withdrawal. In aortic blood obtained during ether anesthesia, AVP-levels were 12- to 560-fold those in control trunk blood. Rapid hemorrhage, 2.0 ml stepwise, resulted in corresponding increases of AVP blood concentration, presumably due to hypothalamohypophyseal ischemia. PRA values showed a similar, albeit less pronounced increase. These results show the importance of controlling conditions of blood sample collection for AVP and PRA analysis, and demonstrate massive release of AVP in response to acute hemorrhage. The amount of AVP released is well about the threshold for pressor activity, and may be of importance in vasoconstrictive adaptation to acute hypovolemic hypotension.
Anesthesia↗
Heymann nephritis-DOCA-NaCl hypertension in the rat. Role of nephritis, DOCA, NaCl, and vascular lesions in the development of hypertension.
In order to explore the impact of nephritis on the development of hypertension, rats with Heymann nephritis were given 0.9% NaCl to drink, in combination with or without DOCA injections, for up to 6 months. Combined nephritis-DOCA-NaCl resulted in severe hypertension and shortened life span, whereas nephritis-NaCl combination failed to induce hypertension or shorten life span. All immunized rats developed membranous glomerulonephritis but creatinine clearance did not decrease. DOCA-NaCl-treated nephritic rats had a heavier proteinuria and more marked renal lesions than NaCl-treated nephritis rats. Proliferative-sclerotic glomerular lesions were seen in the nephritis-DOCA-NaCl group only, correlating to the severity of hypertension. Other renal and extrarenal vascular lesions, increasing with time, also appeared related to the severity of hypertension. This suggests a secondary relationship of vascular damage to hypertension in this model. Appearance of proteinuria preceded the establishment of hypertension, suggesting that nephritis sensitized to the development of hypertension during DOCA-NaCl treatment. Sodium excess alone, however, did not induce hypertension in Heymann nephritic rats. The present Heymann nephritis-DOCA-NaCl hypertension model appears a useful model for the study of hypertension complicating glomerulonephritis.
Animals↗
Age dependence of human plasma renin substrate.
Renin substrate (angiotensinogen) was measured with an assay employing exhaustive incubation of plasma with purified human kidney renin and radioimmunoassay of the angiotensin I (AI) generated. Plasma renin substrate concentration was higher at the age of 3 days (females: 2028 +/- 551, males: 1951 +/- 565 micrograms AI/l, mean +/- SD) than in age group 0-15 years (females: 1513 +/- 555, males: 1263 +/- 392 micrograms AI/l). Plasma renin substrate concentration at the age over 15 years (females: 1780 +/- 464, males 1752 +/- 321 micrograms AI/l) was higher than in children 0-15 years. Expectedly, high concentrations of plasma renin substrate were found in pregnant women at term (4127 +/- 1961 micrograms AI/l).
Adolescent↗