Release of catecholamines in the locus coeruleus of freely moving and anaesthetized normotensive and spontaneously hypertensive rats: effects of cardiovascular changes and tail pinch

Abstract

Noradrenaline turnover has been found to be increased in the locus coeruleus of young spontaneously hypertensive rats (SHR). There is also evidence that the noradrenergic projection from the locus coeruleus to the posterior hypothalamus contributes to the development of genetic hypertension. To investigate whether the release of noradrenaline and dopamine in the locus coeruleus is modified in genetic hypertension, this brain region of adult SHR and normotensive Wistar-Kyoto (WKY) rats was superfused with artificial cerebrospinal fluid through a push-pull cannula. Dopamine and noradrenaline released in the superfusate were determined radioenzymatically. There was no difference in the basal release of noradrenaline and dopamine in the locus coeruleus of conscious, anaesthetized or diazepam-treated adult WKY rats and SHR. In conscious animals, a rise in blood pressure elicited by intravenous infusion of phenylephrine enhanced the release of noradrenaline and dopamine in both strains to the same extent. Intravenous infusion of sodium nitroprusside elicited a fall in blood pressure and also increased to the same degree the release of noradrenaline and dopamine in the locus coeruleus of normotensive and hypertensive conscious rats. In anaesthetized rats, baroreceptor activation by phenylephrine decreased the release of noradrenaline and dopamine, while sodium nitroprusside lowered blood pressure and enhanced the release rates of the two catecholamines. Treatment of conscious rats with diazepam (10 mg/kg, i.p., 120 min prior to starting collection of the superfusate) abolished the phenylephrine-evoked release of catecholamines observed in conscious animals. The sensory stimulus tail pinch led to a slight increase in blood pressure. In conscious animals, this aversive stimulus led to enhanced release of noradrenaline and dopamine that lasted longer in SHR than in WKY rats. The release of catecholamines evoked by tail pinch was abolished in rats treated with diazepam, as well as in anaesthetized animals. Our findings show that in adult rats, genetic hypertension does not modify the release of noradrenaline and dopamine in the locus coeruleus. Since in anaesthetized rats increases in blood pressure diminish, while decreases in blood pressure enhance, the release of noradrenaline and dopamine, it seems that both amines possess a counteracting, hypertensive function in the rat locus coeruleus. When baroreceptor activation by phenylephrine is carried out on conscious animals, stress predominates and the release of catecholamines is enhanced. This study demonstrates the importance of the noradrenergic system of the locus coeruleus in central cardiovascular control and in emotional, stress and pain-regulating processes.

Paraventricular nucleus of the human hypothalamus in primary hypertension: Activation of corticotropin‐releasing hormone neurons

“…In addition, increased release of NA into the PVN was revealed in SHRs (Versteeg et al, 1976;Wijnen et al, 1977;Winternitz et al, 1984;Qually and Westfall, 1993), and this release was especially prominent during the development phase of hypertension in younger animals (Qually and Westfall, 1993). Such enhanced secretion of NA into the PVN in hypertensive rats might be caused by the increased metabolic activity in catecholaminergic brainstem nuclei that is found in these animals in normal (Saavedra et al, 1976;Saavedra, 1979;Koulu et al, 1986;Kawasaki et al, 1991) and even more so in stressful (Kaehler et al, 2000) conditions. It is significant that catecholaminergic brainstem nuclei also seem to be substantially activated in humans with essential hypertension, which is reflected by the significantly elevated overflow of NA and dihydroxyphenylglycol (DHPG) from subcortical region into the minor jugular vein seen in these patients (Ferrier et al, 1993).…”

Modulation of physiological reflexes by pain: role of the locus coeruleus

“…Painful stimulation leads to an increase in the expression of Fos, the protein product of the activation of the intermediate early gene c-Fos, a marker of neuronal activity [Bullitt, 1990 (noxious heat and cold, pinch); Pezzone et al, 1993 (electric shock); Palkovits et al, 1995 (subcutaneous formalin injection); Voisin et al, 2005 (electric tooth pulp stimulation); Wang et al, 2009 (colon distension)]. Noxious stimuli evoke an increase in the release of noradrenaline from the LC [Singewald et al, 1999 (air puff, noise stress); Kaehler et al, 2000 (tail pinch); Sajedianfard et al, 2005 (subcutaneous formalin injection)]. A number of neurotransmitters and neuromodulators have been implicated in the modulation of the activation of the LC by noxious stimuli.…”

Locus Coeruleus Lesions Decrease Oxytocin and Vasopressin Release Induced by Hemorrhage

“…Some studies assign them a pressor role [8][9][10] whereas others give them a depressor role [11][12][13] or even suggest no role for that nucleus in such regulation [14,15]. Previous research in our laboratory demonstrated that LC lesions accentuated the hypotensive response to hemorrhage [16].…”