Is osmolality a long-term regulator of renal sympathetic nerve activity in conscious water-deprived rats?

Abstract

Acute increases in osmolality suppress renal sympathetic nerve activity (RSNA). However, it is not known whether prolonged physiological increases in plasma osmolality chronically inhibit RSNA. To address this hypothesis, mean arterial blood pressure (MAP), heart rate (HR), and RSNA were measured during acute normalization of plasma osmolality in conscious rats made hyperosmotic by 48 h of water deprivation. Water deprivation significantly elevated MAP (120 ± 1 vs. 114 ± 3 mmHg, P < 0.05) and plasma osmolality (306 ± 1 vs. 293 ± 1 mosmol/kgH20, P < 0.01). When plasma osmolality was subsequently lowered to normal (−17 ± 1 mosmol/kgH20) with a 2-h (0.12 ml/min) infusion of 5% dextrose in water (5DW), MAP decreased (−11 ± 1 mmHg), and RSNA increased (25 ± 10% baseline). To assess the role of circulating vasopressin in these changes, rats were pretreated with a V1-vasopressin receptor antagonist before infusion of 5DW. The antagonist lowered MAP (−4 ± 1 mmHg) and raised RSNA (31 ± 3% baseline) and HR (25 ± 5 beats/min) in water-deprived rats (all changes P < 0.05). However, V1-vasopressin receptor blockade did not increase RSNA or HR independently of baroreflex responses to decreases in arterial pressure. After V1 blockade, infusion of 5DW lowered blood pressure (−8 ± 1 mmHg) but did not further affect HR or RSNA. An isotonic saline infusion that produced the same volume expansion as 5DW lowered MAP (−5 ± 2 mmHg) and HR (−68 ± 2 beats/min) but had no effect on osmolality or RSNA in water-deprived rats. Finally, 5DW infusion had negligible effects in water-replete animals. In conclusion, these results fail to support the hypothesis that sustained increases in plasma osmolality, either directly or via increased vasopressin, tonically suppress RSNA.