Cardiovascular effects of l-glutamate and tetrodotoxin microinjected into the rostral and caudal ventrolateral medulla in normotensive and spontaneously hypertensive rats

Abstract

The purpose of this study was to compare the responsiveness of the rostral and caudal ventrolateral medulla in spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats to microinjection of l-glutamate, and to estimate tonic output of these areas by microinjecting the neurotoxin tetrodotoxin. Rats were anesthetized with 1.25 g/kg urethane s.c., implanted with arterial (femoral) and venous (femoral) catheters, artificially ventilated and paralyzed with gallamine triethiodide (10 mg/kg). Using a ventral approach to the brainstem, the mean arterial pressure and heart rate responses to microinjection (30 nl) of l-glutamate (1, 10 and 100 mM) and tetrodotoxin (10 μM) into the rostral and caudal ventrolateral medulla were compared in SH ( n = 7) and WKY ( n = 7) groups. Microinjection of l-glutamate into the rostral ventrolateral medulla produced equivalent increases in mean arterial pressure (maximum+33 ± 3and+36 ± 6 mm Hg, SH and WKY groups respectively) and minimal changes in heart rate. Similar administration of l-glutamate into the caudal ventrolateral medulla caused decreases in mean arterial pressure and heart rate; changes in mean arterial pressure were significantly greater in the SH group than in the WKY group (−52.3 ± 2.9 mm Hg for SH,−22.6 ± 2.6 mm Hg for WKY). Bilateral microinjection of tetrodotoxin into the caudal ventrolateral medulla produced significantly larger increases of mean arterial pressure in WKY rats (+8 ± 4vs+46 ± 8 mm Hg for SH vs WKY). These data indicate that SH rats may have a lower tonic activity of neurons in the caudal ventrolateral medulla, resulting in a lower restraining influence on sympathetic outflow in the SH rat. (Supported by: HL 36552 and KY-THRI 5-42078).