Jan Möhring

Plasma ADH in normal long-evans rats and in long-evans rats heterozygous and homozygous for hypothalamic diabetes insipidus

Abstract A radioimmunoassay for the measurement of arginine-vasopressin (AVP) in rat plasma is described. By precipitating plasma proteins with acetone prior to the assay, a blanc value of zero was obtained for plasma of rats with hypothalamic diabetes insipidus (DI). Under ad lib . water intake as well as after 48 hrs of dehydration, AVP concentrations in plasma of rats heterozygous for DI were by roughly 50 % lower than in plasma of normal control rats. In plasma of DI rats no AVP was measurable 24 hrs after withdrawal of water. These data support the notion that DI rats do not produce any AVP and that the heterozygous animals have partial ADH deficiency. - In normal and heterozygous rats, AVP concentrations in plasma obtained at 5 p.m. were lower than in plasma collected at 10 a.m. This might indicate a diurnal fluctuation of plasma AVP concentrations in the rat.

Vasopressin-mediated blood pressure response to intraventricular injection of angiotensin II in the rat

Abstract1.The role of stimulation of argininevasopressin (AVP) release in the blood pressure (BP) response to intracerebroventricular (ivt) injection of angiotensin II (AII) was investigated.2.Ivt injection of AII to normal Long-Evans (LE) rats, which were conscious and unrestrained, induced a dose-related increase of BP in close correlation with the rise of plasma AVP concentrations (r=0.93;y=34.0 log X-14.4). This regression line crossed the X-axis at plasma AVP concentrations found under control conditions.3.In comparison with the correlation obtained after intravenous injection of AVP (r=0.99;y=35.6 log X-46.9), the correlation between BP increase and plasma AVP after ivt AII exhibited a parallel shift to the left by a factor of 7.5.4.When 0.5 ml of a specific AVP antiserum was injected intravenously, the BP response to subsequent ivt injection of AII was completely blocked in 2 of 7 rats tested and reduced by 50% or more in the other 5 rats.5.In Brattleboro rats homozygous for hereditary hypothalamic diabetes insipidus (DI), in which plasma AVP remained undetectable after ivt AII, BP response was reduced by 50–80% in comparison with the response in LE rats. Drinking response, however, was not altered. During spontaneous drinking, DI rats showed a BP increase of similar magnitude as that after the highest dose of ivt AII.6.We conclude that a close relationship exists in normal LE rats between the rise of BP and of plasma AVP after ivt AII; this correlation represents a cause-effect relationship, since after the intravenous injection of AVP antiserum the BP response to ivt AII is markedly or completely blocked; and sensitization to the vasopressor effect of AVP occurs after ivt AII. The BP increase observed in unrestrained DI rats after ivt AII as well as during spontaneous drinking might be related to a general arousal reaction which would be insignificant in normal LE rats.

IS VASOPRESSIN INVOLVED IN THE PATHOGENESIS OF MALIGNANT DESOXYCORTICOSTERONE HYPERTENSION IN RATS

Rats with unilateral nephrectomy were offered 1% sodium chloride as drinking fluid and were injected with desoxycorticosterone trimethylacetate (D.O.C.-T.M.A.) at weekly intervals. During the fourth to seventh week after the start of the experiment, malignant hypertension developed in most of the animals: body weight fell, reflecting volume depletion; serum osmolality and serum sodium and urea concentrations increased; in the kidneys malignant nephrosclerosis occurred. In such animals, plasma concentrations of arginine-vasopressin were increased ten-fold in comparison with control animals; intravenous injection of a specific vasopressin antibody resulted in a transient fall of blood-pressure (B.P.) to normal or subnormal levels, while the injection of an angiotensin-I or angiotensin-II antibody did not affect B.P. In control animals none of the antibodies had an effect on B.P. It is concluded that in the pathogenesis of malignant D.O.C. hypertension vasopressin plays a role similar to that of renin-angiotensin in malignant renal hypertension.

Salt appetite during the early phase of renal hypertension in rats

SummaryIn male Sprague-Dawley rats the left renal artery was constricted by a 0.2 mm silver clip while the contralateral kidney was left untouched. 10 days after clipping the animals were offered, in addition to water, 0.9% saline as drinking fluid for 6 days. Hypertensive animals drank twice as much saline as did control rats throughout the period of observation. In the hypertensive animals, 24-hrs saline intake during the first day of the self-selection study was quantitatively related to the actual height of blood pressure and to the preceding blood pressure increase. After 6 days on the self-selection regimen, plasma angiotensin II concentrations in the hypertensive rats were elevated by 50% when compared with control rats.On the basis of these and previously reported findings (i.e. an increased activity of the renin-angiotensin-aldosterone system and sodium retention) it is suggested: a) despite sodium retention salt appetite is enhanced, indicating a disordered regulation of sodium balance during the early phase of renal hypertension in rats; b) elevated plasma concentrations of angiotensin II and aldosterone could have enhanced salt appetite; c) despite greater salt intake than in control rats the activity of the renin-angiotensin system remains elevated in renal hypertensive rats, thereby possibly inducing a sustained high saline intake.

ADH-induced potassium retention in rats with genetic diabetes insipidus.

Abstract Rats with hereditary hypothalamic diabetes insipidus (D.I.) showed hypokalemia and hypernatremia when compared with normal Wistar rats. After administration of vasopressin tannate to D.I. rats, potassium balance became positive for the subsequent 24 hours, whereas sodium balance was unaffected. In normal control rats ADH had no effect on sodium or potassium balance. Since serum potassium concentration was unchanged 12 hours after ADH injection, it is suggested that the retained potassium is compartmentalized mainly in the intracellular space.

Increases potassium intake and kaliopenic nephropathy in rats with genetic diabetes insipidus

Abstract The recent observations of hypokalemia and of ADH-induced potassium retention in rats with hereditary hypothalamic diabetes insipidus (D.I.) indicated an impaired regulation of potassium balance in such rats. Accordingly, D.I. rats might be expected to have an increased daily requirement of potassium and to show signs of chronic potassium deficiency, e.g. kaliopenic nephropathy. When demineralized water, isotonic NaCl, and isotonic KCl were offered simultaneously, D.I. rats showed a marked preference for the KCl; control rats drank virtually none. The kidneys of D.I. rats showed the histo-pathologic picture of kaliopenic nephropathy, i.e. vacuolar degeneration of tubular cells.

The juxtaglomerular apparatus of rats with hereditary hypothalamic diabetes insipidus

SummaryThe juxtaglomerular apparatus (JGA) of rats with hereditary hypothalamic diabetes insipidus (DI) was studied. Plasma concentration of renin and angiotensin II, as well as serum sodium concentration and serum osmolality of DI rats are elevated. The morphological examination reveals no characteristic alteration of the epitheloid cells. The results show that the epitheloid cells are sufficiently adapted for the higher release of renin.

Zum extrahepatischen Stoffwechsel von Aldosteron

SummaryIn stop flow experiments during infusion of 1,2-3H-18-aldosterone glucuronide there was no proximal tubular secretion of this metabolite in contrary to experiments during infusion of 1,2-3H-aldosterone. The discrepancy must be explained by formation of 1,2-3H-aldosterone glucuronide out of3H-aldosterone in proximal tubular cells, while the 1,2-3H-18-aldosterone glucuronide in the plasma of the renal artery blood is only filtered in the glomerulum.ZusammenfassungMit Stop flow-Versuchen an Hunden konnten wir nach Infusion von 1,2-3H-18-Aldosteronglucuronid im Gegensatz zur Infusion von freiem 1,2-3H-Aldosteron keine proximale Sekretion von 1,2-3H-18-Aldosteronglucuronid nachweisen. Daraus kann geschlossen werden, daß in Hundenieren die proximalen Tubuluszellen wohl 18-Aldosteronglucuronid aus Aldosteron bilden und an das Tubuluslumen abgeben, während im Nierenarterienblut vorhandenes 18-Aldosteronglucuronid nur glomerulär filtriert und ausgeschieden wird.