Hiro Amano

Caudal ventrolateral medulla

SummaryWe localized glutamate-sensitive sites in the ventrolateral medulla of the rat with the spinal cord cut at C1. When unilaterally injected into a circumscribed region of the caudal ventrolateral medulla,l-glutamate (30–300 ng) elicited a dose-dependent increase in arterial pressure. The pressor response was accounted for by an increased release of vasopressin because it was abolished by the intravenous injection of a vasopressin antagonist. Bilateral microinjections of kainic acid (50 ng) into the ventrolateral glutamate-sensitive area markedly reduced a vasopressin-induced pressor response to kainic acid (30 ng), injected bilaterally into the nucleus tractus solitarii. It is concluded that the glutamate-sensitive neurons in the caudal ventrolateral medulla are involved in mediation of the vasopressin-induced pressor response arising from the nucleus tractus solitarii.

Evidence for tonic activation of prejunctional β‐adrenoceptors in guinea‐pig pulmonary arteries by adrenaline derived from the adrenal medulla

1 The effects of (+)‐carteolol 10−8 m to 10−6 m, a non‐selective β‐antagonist, applied cumulatively, on stimulation‐evoked 3H‐release at 1 Hz were studied in pulmonary arteries isolated from guinea‐pigs. The guinea‐pigs were subjected to either bilateral adrenalectomy, adrenalectomy followed by injections of deoxycorticosterone acetate (DOCA) and hydrocortisone, bilateral adrenodemedullation or a sham operation, and then loaded in vitro with [3H]‐noradrenaline. 2 Carteolol inhibited 3H‐output in arteries from sham‐operated animals in a concentration‐dependent manner. This inhibitory effect was not found in pulmonary arteries from animals subjected to adrenalectomy or adrenodemedullation. However, DOCA and hydrocortisone pretreatment, did not prevent the disappearance of the carteolol‐induced inhibition of 3H‐release. 3 Adrenalectomy and adrenodemedullation depleted or markedly reduced the endogenous contents of adrenaline in pulmonary arteries without altering the levels of dopamine and noradrenaline. 4 It is concluded that adrenaline, mainly derived from the adrenal medulla, acts as an endogenous agonist for tonically functioning prejunctional β‐adrenoceptors in guinea‐pig pulmonary arteries, probably by being taken up and co‐released with noradrenaline.

Involvement of central catecholamines in mediation of pressor responses of the rat to carotid occlusion

SummaryCarotid occlusion evoked a pressor response in rats after transection of the spinal cord. Intraventricular pretreatment with 6-hydroxydopamine inhibited the pressor response. The pressor response to occlusion was also diminished by the intraventricular but not by the intravenous injection of guanethidine. Intravenous atropine or mecamylamine, or intraventricular captopril did not affect the pressor response. Thus, it appears that central catecholaminergic mechanisms are involved in the mediation of the pressor response to carotid occlusion.

Vasopressin-induced pressor responses to carotid occlusion in the rat

SummaryWe studied the effect of carotid occlusion on blood pressure in cordotomized rats. Occlusion of both common carotid arteries resulted in an increase in blood pressure. This response was unaffected by denervation of the sinus and aortic nerves, and vagi. The response to occlusion was blocked by intravenous administration of a vasopressin antagonist, d(CH2)5 Tyr(Me)arginine-vasopressin, but not by intravenous administration of hexamethonium or captopril. Further, microinjection of procaine into the paraventricular nuclei abolished the pressor response to occlusion. Thus, it appears that in cordotomized rats carotid occlusion causes release of vasopressin and this in turn results in an elevation of blood pressure. The arterial baroreceptors are not essential for the pressor response.

Adrenaline as an endogenous agonist for presynaptic beta-adrenoceptors and their relevance to the development of hypertension in spontaneously hypertensive rats.

We attempted to identify an endogenous agonist for presynaptic facilitatory β-adrenoceptors. Pulmonary arteries isolated from guinea pigs 5 days after bilateral adrenalectomy and renal arteries from 4-week-old spontaneously hypertensive rats (SHR) exposed to swimming stress for 1 h were preloaded with 3H-noradrenaline and superfused with Krebs medium. Electrical field stimulation was carried out four times at 15-min intervals (S1 to S4). Beta-antagonist carteolol at 10-8, 10-7 and 10-6 mol/l was cumulatively applied after S1, S2 and S3 and the effect was estimated as the evoked 3H release ratio, Sx:S1. Catecholamine contents in arteries were measured by high performance liquid chromatography with electron capture. In sham-operated pulmonary arteries, carteolol inhibited evoked 3H release in a concentration-dependent manner. This inhibition was completely abolished by adrenalectomy. Adrenalectomy depleted adrenaline contents without modification of noradrenaline and dopamine. In renal arteries, swimming stress potentiated carteolol-induced concentration-dependent inhibition of evoked 3H release and increased adrenaline and dopamine contents without modification of noradrenaline. Adrenaline derived from adrenals and probably stored and coreleased with noradrenaline acts as an endogenous agonist for presynaptic β-adrenoceptors.

Effect of Nicotine on the Turnover Rate of Catecholamine in the Rat Brain

Acute effects of in vivo nicotine application on turnover rates of dopamine (DA), norepinephrine (NE), and epinephrine (EP) in the rat brain regions were examined. Turnover rates of the amines were evaluated by measuring tissue content of a metabolite of DA and NE, dihydroxyphenylacetic acid and 3-methoxy-4-hydroxyphenylethylene glycol, respectively, and/or by comparing decline of contents of the amines after blockade of synthesis. Synthesis was blocked by α-methyl-p-tyrosine 300 mg/kg, i.p., and fusaric acid 80 mg/kg, i.p., an inhibitor of tyrosine hydroxylase and dopamine-β-hydroxylase, respectively. Three kinds of the amines and the metabolites were measured using HPLC-ECD methods. Injection of nicotine (0.4–1.0 mg/kg, s.c.) increased DA turnover rate in hypothalamus, thalamus, and pons/medulla, and NE turnover rate in striatum, hypothalamus, thalamus, midbrain, pons/medulla, and cerebellum. As a parameter of turnover rate, nicotine-induced increases in content of the metabolites were more sensitively detected than nicotine-induced decreases in DA and NE content itself after blockade of synthesis. These facilitatory effects of nicotine on turnover rate of DA and NE were antagonized by pretreatment with mecamylamine 5 mg/kg, i.p., a centrally acting nicotinic antagonist, but not by hexamethonium 10 mg/kg, i.p., an antagonist poorly penetrating into the brain. Nicotine also tended to accelerate the disappearance of EP content caused by fusaric acid in hypothalamus, thalamus, midbrain, and pons/medulla. These findings demonstrate that nicotine increases the turnover rate of catecholaminergic neurons in various regions via direct activation of central nicotinic receptors.