Effect of head-up tilt on vasopressin secretion and arterial pressure in anesthetized rats.

The effect of 45 or 60 degrees head-up tilt on plasma arginine vasopressin (AVP) concentration, mean arterial pressure, and heart rate was studied in inactin-anesthetized rats. In all rats, there was a fall in blood pressure that was maximal within about 20-40 s and then returned toward normal. After 45 degrees head-up tilt for 30 min, AVP was increased from 7.0 +/- 1.7 to 21.0 +/- 5.9 pg/ml. Sixty-degree head-up tilt increased AVP at 5, 15, and 30 min, respectively, from 10.6 +/- 2.9 to 22.1 +/- 4.8 pg/ml, from 10.6 +/- 2.5 to 28.5 +/- 5.3, and from 16.1 +/- 4.7 to 62.6 +/- 10.3 pg/ml. After bilateral cervical vagotomy, 60 degrees head-up tilt for 30 min increased AVP, but the change was significantly reduced compared to intact animals. Bilateral sinoaortic denervation increased basal values of AVP, and there was no further increase during tilt. Bilateral electrolytic lesions of the hypothalamic paraventricular nuclei caused only a moderate reduction in the AVP response to tilt. When the effect of endogenous angiotensin II was antagonized by saralasin or its production was blocked by enalapril, the AVP response to tilt was reduced. The mean arterial pressure fell during the 1st min, but recovered rapidly when rats treated with a V1 vasopressin receptor antagonist were tilted. The data indicate that head-up tilt increases AVP secretion in anesthetized rats, that the response is mediated by the vagus and particularly by the arterial baroreceptors, and that circulating angiotensin II contributes to the response. However, the increased circulating AVP is not necessary for the maintenance of arterial pressure.

Lack of effect of vasopressin replacement on renin hypersecretion in Brattleboro rats.

To determine how the vasopressin deficiency in homozygous Brattleboro rats with diabetes insipidus produces increased renin secretion, homozygous and heterozygous Brattleboro rats were infused through subcutaneously implanted Alzet minipumps for 1 wk with a dose of arginine vasopressin that restored plasma vasopressin to normal in the homozygous animals. In the homozygous animals, plasma renin activity (PRA) and the PRA response to immobilization remained elevated compared with Long-Evans controls. Propranolol reduced PRA to normal and markedly reduced the PRA response to immobilization. PRA was normal in heterozygous Brattleboro rats. The data indicate that the increased renin secretion in homozygous rats is a result of increased sympathetic activity, and because circulating vasopressin does not cross the blood-brain barrier, it seems likely that the increased sympathetic activity is central in origin.

Pharmacological evidence that the sympathetic nervous system mediates the increase in renin secretion produced by immobilization and head-up tilt in rats.

To determine the mechanism by which immobilization and head-up tilt under inactin anesthesia increase plasma renin activity (PRA), the effect of these stimuli on plasma levels of vasoactive intestinal polypeptide (VIP) were measured and the effect of the beta-adrenergic blocking drug, propranolol on the response of plasma renin activity determined. Increases in circulating VIP are known to stimulate secretion of renin. After 10 min of immobilization, plasma renin activity was increased and VIP in plasma was unchanged. After 30 min of tilting, plasma renin activity was also increased and VIP in plasma was unchanged. The increases in plasma renin activity were blocked by propranolol. Inactin anesthesia by itself increased plasma renin activity and this response was unaffected by propranolol and associated with a small decrease, rather than an increase in VIP in plasma. The results indicate that the responses of plasma renin activity to immobilization and head-up tilt are due to increased secretion of renin mediated by the sympathetic nervous system. On the other hand, the increase in secretion of renin produced by inactin anesthesia does not appear to be mediated by the sympathetic nervous system. There was no evidence that VIP was responsible for any of the increases.

Relation of the ventromedial nuclei of the hypothalamus to the regulation of renin secretion.

During an investigation of the role of the mediobasal hypothalamus in the regulation of renin secretion from the kidneys, we found that lesions of the ventromedial nuclei prevented the increase in plasma renin activity produced by p-chloroamphetamine. In the present study, we tested the effects of bilateral electrolytic lesions of the ventromedial nuclei on the increase in plasma renin activity produced in sham-operated rats by immobilization, head-up tilt under inactin anesthesia, and a low-sodium diet. Ventromedial lesions reduced or abolished the plasma renin activity increase to all three stimuli without any change in plasma angiotensinogen. The plasma renin concentration responses to immobilization and a low-sodium diet were also reduced. All these stimuli probably exert their effect by way of the sympathetic nervous system. The data support the hypothesis that the ventromedial nuclei or neural fibers passing through them are important in the renin response to diverse stimuli that act by way of sympathetic discharge.