Elevated sympathetic outflow in hypovolemic rats depends upon the tonic activity of RVLM neurons

Abstract

Elevated sympathetic outflow contributes to the maintenance of arterial blood pressure (ABP) during hypovolemia. The neural mechanisms underlying this response are not completely understood but likely involve neurons in the rostral ventrolateral medulla (RVLM). To test this hypothesis, male Sprague-Dawley rats (300–325 g) were made hypovolemic by an injection of furosemide (10 mg/kg, sc) and denied access to food and water. Control rats received an injection of isotonic saline (1 ml/kg, sc). Two hours later, rats were anesthetized with inactin (100 mg/kg, ip) and the RVLM was inhibited bilaterally with microinjection of the GABAA receptor agonist muscimol (100 pmol per 50 nl per side). Bilateral inhibition of the RVLM produced a significantly greater decrease in mean ABP of furosemide-treated rats versus control rats (50±3 vs 36±3 mmHg, respectively; P<0.05, n=4 per group) although baseline mean ABP was not different (99±3 vs 102±2 mmHg, respectively). Administration of the ganglionic blocker hexamethonium (30 mg/kg, iv) produced a significantly greater fall in mean ABP of furosemide-treated rats versus control rats (47±3 vs 35±2 mmHg, respectively; P<0.05, n=4 per group). As expected, furosemide treatment significantly increased hematocrit (51±1 vs 44±1%, P<0.05) and plasma protein concentration (7.3±0.1 vs 5.8±0.2 g/dl, P<0.01) but did not alter plasma osmolality (298±3 vs 298±2 mOsm/kg). These findings suggest that sympathetic outflow contributes more to the maintenance of ABP in hypovolemic rats and this depends, at least partly, on the tonic activity of RVLM neurons. Supported by NIH HL073661 and University of Kentucky College of Medicine.