Release of catecholamines in the locus coeruleus of freely moving and anaesthetized normotensive and spontaneously hypertensive rats: effects of cardiovascular changes and tail pinch.
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.
Kaehler
S T
ST
Institut für Pharmakologie und Toxikologie der Universität Innsbruck, Austria. Pharmako-Toxiko@uibk.ac.at
Sinner
C
C
Philippu
A
A
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008125:Locus Coeruleus / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D010812:Physical Stimulation; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity; D013623:Tail / Q000502:physiology
D009599:Nitroprusside; D010656:Phenylephrine; D004298:Dopamine; D009638:Norepinephrine