DIFFERENTIAL ALTERATION OF NEURONAL AND CARDIOVASCULAR-RESPONSES TO ADENOSINE MICROINJECTED INTO THE NUCLEUS-TRACTUS-SOLITARIUS OF SPONTANEOUSLY HYPERTENSIVE RATS

We previously reported that adenosine elicited site-dependent neuronal and cardiovascular responses in two subareas of the nucleus tractus s olitarius (NTS) of normotensive rats. Pressor and tachycardic response s were obtained from the rostral NTS (adenosine presser system), and d epressor and bradycardic responses were obtained from the caudal NTS ( adenosine depressor system). In both areas, adenosine inhibited the fi ring rate of barosensitive neurons. The present study investigated whe ther spontaneously hypertensive rats (SHR) exhibit abnormal neuronal a nd cardiovascular responses mediated by the adenosine presser and depr essor systems within the NTS. Male SHR and Wistar-Kyoto rats (WKY) wer e anesthetized with urethane and prepared for blood pressure and heart rate recording, stereotaxic microinjection of adenosine into the NTS, and extracellular recording of single-unit neuronal activity of NTS n eurons. Chemical identification of the targeted neuronal pool was made by L-glutamate (5 nmol) and confirmed by histology. SHR exhibited sig nificantly higher mean arterial pressure and firing rate of caudal NTS neurons (45.0+/-4.5 versus 27.3+/-4.7 spikes per 2.5 seconds, P<.05) but similar heart rate and neuronal firing rate of rostral NTS neurons compared with WKY. Adenosine (0.1, 1, and 10 nmol) elicited dose-rela ted neuronal and cardiovascular responses in both strains. However, SH R exhibited differential alterations in both adenosine systems. Compar ed with WKY, SHR exhibited attenuated presser, tachycardic, and neuron al responses medi ated by the adenosine presser system and exaggerated depres sor, bradycardic, and neuronal responses mediated by the adeno sine depressor system. In both strains, the responses elicited by aden osine were virtually abolished by theophylline (10 mg/kg IV), suggesti ng that these responses were mediated by adenosine receptors in the NT S. Furthermore, the theophylline-evoked increase in blood pressure was twofold higher in SHR (15.0+/-1.7 versus 6.9+/-1.5 mm Hg, P<.05); lar ger but nonsignificant increases in heart rate and neuronal firing rat e also were evident in SHR compared with WKY. These findings suggest d ifferential alterations in adenosine presser and depressor systems in the NTS of SHR, which may be implicated in the pathophysiology of this model of hypertension.