Hypotensive response in spontaneously hypertensive rats following microinjection of α-methylnoradrenaline in the caudal brain-stem

Abstract

SUMMARYLocal microinjection of 1.25 nmol (-)-a-methylnoradrenaline in the Arregion of the nucleus tractus solitarii (NTS) caused a decrease of blood pressure and heart rate in both spontaneous hypertensive rats (SHR) and Wistar-Kyoto (W/K) rats. Although the maximal responses in both strains did not differ, the decrease in blood pressure lasted longer in the SHR. These results do not support the concept of a diminished sensitivity of catecholaminergic receptors in the NTS of SHR to a-methylnoradrenaline.We have shown that the local administration of various catecholamines to the A2-region of the nucleus tractus solitarii (NTS) dose-dependently decreased the blood pressure and heart rate of a normotensive strain of Wistar rats [1,9,10]. A dysfunction of catecholaminergic transmission has been suggested to play a role in the development of hypertension in SHR [8]. We therefore tested whether the effect on blood pressure and heart rate differed in SHR and W/K rats following the microinjection of a-methylnoradrenaline into the A2-region of the NTS of the medulla oblongata.Male spontaneously hypertensive rats (SHR-NIH Cpb) were used with Wistar-Kyoto rats (W/K-NIH Cpb) as normotensive controls (19 weeks old) (for genealogy see [2]). All rats were obtained from the Centraal Proefdierenbedrijf TNO, Zeist, The Netherlands.The rats were anesthetized with pentobarbital (25 mg/kg) given i.p. with a supplemental dose (2.5 mg/kg i.v.) as described by Judy et al. [3]. These authors showed that such doses of pentobarbital did not materially affect Address correspondence to: P. Zandberg

GPCR dimerization in brainstem nuclei contributes to the development of hypertension

“…We found that the hypotensive effects of activating α 2 ‐adrenoceptors via an intra‐NTS guanfacine microinjection were attenuated in hypertensive SHRs (Figure A), whereas Zandberg and de Jong did not find a difference between SHRs and WKY rats using a microinjection of α‐methylnoradrenaline into the NTS (Zandberg and de Jong, ). This difference might reflect the activity of α‐methylnoradrenaline as an agonist at β‐adrenoceptors (De Jong and Nijkamp, ) and the higher affinity of guanfacine for α 2A ‐adrenoceptors (Uhlen and Wikberg, ; Kanagy, ).…”