R. E. Shade

Pressor responsiveness to vasopressin in the rat with DOC-salt hypertension.

SUMMARY To further characterize the role of rasopressin in DOC-salt hypertension, four groups of unilaterally nephrectomized rats were studied: control rats giren no further treatment, rats treated with DOC and giren 1% saline to drink, or rats treated with only DOC, or 1% saline. Only rats treated with DOC or DOC- salt became hypertensive. Control rats and rats treated with only DOC or 1% saline had similar pressor responses to exogenous rasopressin and angiotensin II. Within the DOC-salt group, two populations of rats were identified: one with normal pressor responsiveness to rasopressin, and one with markedly enhanced pressor responsireness to rasopressin. Incidence of enhanced responsiveness increased with duration of treatment. Urinary excretion of rasopressin was elerated in the 1% saline and DOC-salt groups after 1 week of treatment, and in the DOC group after 4 weeks. Howerer, the plasma rasopressin concentration was elerated only in the rats treated with both DOC and saline. It is suggested that rasopressin is essential for the expansion of blood rolume in the early stages of DOC-salt hypertension, and functions as a direct pressor agent only in the later stages.

The Effect of Intracerebroventricular Indomethacin on Osmotically Stimulated Vasopressin Release

Experiments were carried out to investigate the effect of intracerebroventricular administration of a prostaglandin synthesis inhibitor on the osmotic control of vasopressin (ADH) secretion. During ventriculocisternal perfusion with indomethacin (7.6 microgram/min) or vehicle, dogs were infused intravenously with either 2.5 or 0.15 M NaCl. Hypertonic saline infusion elevated plasma osmolality approximately 60 mosm/kg H2O. In accordance, the plasma ADH concentration increased substantially in animals perfused ventriculocisternally with the vehicle (from 2.1 +/- 0.7 to 7.3 +/- 1.3 microU/ml); this response was markedly attenuated, however, in animals perfused with indomethacin (from 1.0 +/- 0.2 to 2.2 +/- 0.4 microU/ml). Isotonic saline infusion caused a decline in plasma ADH concentration which was similar in the indomethacin- and vehicle-perfused groups. Mean arterial blood pressure was unchanged during the experiments. In a companion study, ventriculocisternal perfusion with 152 ng PGE2/min was found to be as effective in stimulating ADH release in the presence of indomethacin as in its absence, indicating that the action of indomethacin in the first study was not nonspecific. The suppression of osmotically induced ADH release by intracerebroventricular indomethacin suggests that endogenous brain prostaglandins play a critical intermediary role in the osmotic control of ADH secretion.

Vasopressin in the rat with partial nephrectomy-salt hypertension

The role of vasopressin in the pathogenesis of partial nephrectomy (PN)-salt hypertension was examined in the rat. Hypertension was produced by reducing renal mass 70% and substituting 1% saline for drinking water 2 to 4 days after surgery. PN alone resulted in an increase in systolic blood pressure. Subsequent salt loading led to a further large increase in arterial pressure. On the second to third day after substitution of saline for drinking water, urinary vasopressin excretion (UADHV) was increased six-fold and the plasma vasopressin concentration was increased two and one-half-fold. UADHV then fell to a level that was three-fold greater than control values 5 days later. Although there was a marked stimulation of vasopressin release during the period of salt loading, a vasopressin pressor antagonist had only a small effect on arterial pressure. This suggests vasopressin is not a major pressor agent in PN-salt hypertension.

One-Clip, One-Kidney Hypertension in Rats with Hereditary Hypothalamic Diabetes Insipidus

An attempt was made to produce one-clip, one-kidney hypertension in the rat with diabetes insipidus (DI). Renal artery constriction in unilaterally nephrectomized DI rats (DI-clip) resulted in an increased blood pressure in all 9 rats, but this response was only transient in 3 rats. The magnitude of the hypertension was less in the DI-clip rats than in Long-Evans rats subjected to the same protocol (LE-clip). Infusion of saralasin i.v. at doses of 10 and 30 micrograms/kg . min. 4 to 6 weeks after surgery was without effect on mean arterial pressure in LE-clip and control DI rats, but substantially lowered blood pressure in the DI-clip rats (p less that 0.05 - 0.01). It is concluded that vasopressin is not essential for the production of one-clip, one kidney hypertension in the rat, and that, in the DI rat, the renin-angiotensin system is an important factor in this form of hypertension.

1139 PARATHYROID (PTH) AND ANTIDIURETIC HORMONE (ADH) IN REYE-JOHNSON SYNDROME (RJS)

From the metabolic standpoint, several features of RJS implicate a role for cAMP in the pathophysiology of this disease. ↑ plasma cAMP is found in RJS to corroborate this possibility. In the presence of a normal degrading system, cAMP should not be expected to be ↑ in the urine. However, 25% of cases have ↑ cAMP excretion. Since PTH and ADH are both known to ↑ cAMP production by the cells of the renal tubules, these hormones were measured in plasma, retrospectively, in untreated RJS patients. ↑ ADH and PTH levels were found which correlated with the severity of the disease. In two patients, a rapid decline in the PTH levels was seen in 3-5 hours. No significant changes in serum Ca, Mg, PO4, and osmolality were noted. These findings add two more hormones in addition to insulin, glucagon, ACTH, cortisol, GH, prolactin, and the catecholamines which are increased in the complexity of findings in RJS. A model which could accommodate some of these findings and lend insight to a possible mechanism involving Ca translocation whereby an underlying membrane lesion might be further aggravated by these abnormalities is proposed.This work was supported in part by a grant from the USPHS, NIH HD 11657.