Effect of catecholamine-receptor stimulating agents on blood pressure after local application in the nucleus tractus solitarii of the medulla oblongata

Abstract

Effect of catecholamine-receptor stimulating agents on blood pressure after local application in the nucleus tractus solitarii of the medulla oblongata, European J. Pharmacol. 55 (1979) 43--56.The effect of various catecholamines and a-mimetics, given by microinjection in the A2-region of the nucleus tractus solitarii (NTS), on blood pressure was investigated in anesthetized male rats. A dose-dependent decrease of blood pressure and heart rate was induced by adrenaline as the most effective drug, followed by noradrenaline, dopamine, a-methylnoradrenaline and octopamine. Ablation of the rostral or caudal part of the NTS, or removal of the area postrema did not diminish the effect of a-methylnoradrenaline. Higher doses of noradrenaline and a-methylnoradrenaline caused an initial rise of blood pressure, while the blood pressure lowering effect of noradrenaline was diminished, and that of a-methylnoradrenaline and dopamine delayed. Isoprenaline and the (+)-stereoisomers of noradrenaline and a-methylnoradrenaline were ineffective. The hypotensive effect of dopamine was not prevented by systemic injection of the dopamine ~-hydroxylase inhibitor FLA 63. Prior application of haloperidol, yohimbine and phentolamine antagonized the hypotensive response to dopamine and a-methylnoradrenaline. Application of peripherally effective a-mimetics into the A2-region had no or little effect, while high doses increased blood pressure. Tyramine and clonidine caused some decrease of blood pressure. Clonidine also decreased blood pressure when it was applied in the area of the locus coeruleus. Application of isoprenaline in the locus coeruleus also decreased blood pressure while in contrast adrenaline, noradrenaline, dopamine and 0l-methylnoradrenaline increased blood pressure. The present data suggest that the catecholaminergic receptors in the A2-region of the NTS differ from the classic vascular a-receptor and that the NTS also may contain structures which can antagonize the decrease in blood pressure. Catecholamines a-Mimetics Locus coeruleusDecrease of blood pressure Nucleus tractus solitarii

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

“…The hypotensive effect however lasted longer in SHR than in W/K rats, after both unilateral and bilateral application. The pattern of the blood pressure response of the W/K rat was comparable to that of the normal Wistar rat [10]. In SHR the maximal decrease in heart rate 5 min after injection was -28 + 8 bpm and -61 + 10 bpm following unilateral and bilateral application respectively.…”

“…Unilateral as well as bilateral injections of (-)-~-methylnoradrenaline (1.25 nmol) into the A2-region of the NTS caused a significant decrease in blood pressure and heart rate in SHR and W/K rats. Maximal effects on both blood pressure and heart rate were obtained within 5--10 min following injection as had been seen in normotensive Wistar rats anesthetized with urethane [10]. After bilateral administration of (-)-~-methylnoradrenaline {2 × 1.25 nmol) the decrease in blood pressure in both groups of rats was more pronounced than after unilateral administration.…”

“…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].…”

Effect of N,N-dimethyl-p-methoxyphenylethylamine on blood pressure and brain catecholamines in doca-saline hypertensive rats

“…The experiments began 4 weeks after implantation of DOCA (body weight 250-300 g). Blood pressure was measured frequently in the chronic experiments using an indi-rect tail-sphygmographic method (Leenen and De Jong, 1971) and direct measurement via a cannula in the femoral artery as described by Zandberg et al (1979). Plastic cannulas were implanted into the lateral ventricle using the stereotactic coordinates of KOnig and Klippel (1967).…”

“…injections, 300 #g were dissolved in 1/tl. Local microinjections were given in a volume of 0.4 /,1 (Zandberg et al, 1979).…”