Yoshinobu Numao

A1 noradrenergic neurons tonically inhibit sympathoexcitatory neurons of C1 area in rat brainstem

In rats anesthetized with urethane and paralyzed, bilateral microinjections of kainic acid (KA) into the region of caudal ventrolateral medulla (CVL) containing noradrenergic neurons of the A1 group (A1 area) elicited a decrease followed by an increase in arterial pressure (AP), heart rate (HR) and sympathetic renal nerve activity (RNA). The sympathoinhibitory and sympathoexcitatory effects of KA were prevented by bilateral microinjection of tetrodotoxin into an area of the rostral ventrolateral medulla (RVL) containing C1 adrenergic neurons (the C1 area). In contrast, the autonomic responses were not altered by interruption of the two other principal projections of A1 area neurons, namely to the hypothalamus or to the nucleus tractus solitarii. Bilateral microinjections of tyramine, clonidine, alpha-methylnoradrenaline or histamine into the C1 area elicited a dose-dependent, anatomically specific and reversible decrease in AP, HR and RNA. The effect of tyramine was blocked by previous microinjection of reserpine, 6-hydroxydopamine (6-OHDA), or phentolamine into the C1 area. Pretreatment with phentolamine unveiled a hypertensive effect of alpha-methylnoradrenaline. All effects of alpha-methylnoradrenaline were blocked by pretreatment of the C1 area with phentolamine plus DL-propranolol, whereas those elicited by histamine prevailed. Pretreatment of the C1 area with 6-OHDA abolished all changes in AP and HR elicited by microinjections of KA into the A1 area. We conclude that (1) neurons of the CVL tonically inhibit sympathetic activity, (2) this effect is mediated by an action upon vasomotor neurons of the C1 area of RVL, (3) the inhibition is mediated by noradrenergic projections from A1 neurons into the C1 area, and (4) this tonic sympathoinhibitory effect is independent of the baroreceptor reflex.

CENTRAL RESPIRATORY DRIVE-RELATED ACTIVITY IN SYMPATHETIC-NERVES OF THE RAT - THE REGIONAL DIFFERENCES

In halothane-anaesthetized, vagotomized, SA-denervated rats, the activity of various sympathetic nerves has been analyzed with respect to phrenic nerve discharge (an indicator of central respiratory drive (CRD)). The cervical and lumbar sympathetic nerves had maximal activity following, and were least active during phrenic nerve discharge. In contrast, the splanchnic, cardiac, renal and adrenal nerves exhibited their activity peak during phrenic nerve discharge (i.e. inspiration). Similar activity profiles were observed after ganglion blockade in the mixed pre- and postganglionic fibre preparations. These observations indicate that it is the subpopulations of preganglionic neurones and the proportional contribution of each to whole-nerve activity which give rise to the differences in CRD-related activity profiles between nerves.

The aortic nerve-sympathetic reflex in the rat

Abstract The effects of stimulation of aortic nerve A- and C-fibers on the renal and cardiac sympathetic nerve activities in anesthetized and immobilized Sprague-Dawley rats were investigated. A separate aortic nerve was found in 46 rats (90%) out of 51. Activation of A- and C-fiber groups, alone or in combination, resulted in an inhibition of renal and cardiac nerve activities. However, an excitatory component preceding the inhibitory component, representing the reflex response to stimulation of non-barosensory afferent fibers contained in the carotid sinus or aortic nerve, was never observed. This results provides electrophysiological evidence supporting the view that the rats aortic nerve does not contain a significant amount of functionally active non-barosensory afferents. As with the aortic nerve relfex in the rabbit and cat, the sympatho-inhibitory action of C-fibers was more powerful and longer-lasting than that of A-fibers. Furthermore, the C-fiber reflex was elicited at stimulus frequencies as low as 2 Hz. No significant difference was found between the reflex response of cardiac and renal nerves. On the other hand, stimulation of the superior laryngeal nerve, which constitutes an important pathway carrying arterial baroreceptor fibers, caused a reflex sympathetic response typically consisting of excitatory and inhibitory components. Thus, the rats aortic nerve provides a useful experimental means to activate selectively central neural structures associated with barosensory afferents and to elicit the reflex response homologous to that in the arterial baroreceptor reflex in rabbits and cats.

Physiological and pharmalogical properties of the three subsystems constituting the aortic nerve-renal sympathetic reflex in rabbits

Electrical stimulation of the aortic nerve of anesthetized rabbits reflexly evoked both excitation and inhibition of renal nerve activity. The excitatory component of the reflex, observed in about 75% of the animals, was elicited by activation of aortic C-fibers. It was selectively suppressed by chronic treatment of the animal with capsaicin. Intracisternal injection of either [D-ala2]-met-enkephalinamide or beta-endorphin markedly attenuated this excitatory component, although neither affected the excitatory component mediated by chemoreceptor fibers in response to stimulation of the carotid sinus nerve. It seems most likely that nociceptive C-fibers of the rabbits aortic nerve were responsible for the excitatory component. On the other hand, the inhibitory component was reflexly elicited by stimulation of the aortic A- or C-fiber group activated separately or in combination. In agreement with previous reports, the sympatho-inhibitory action of C-fibers was more powerful and longer-lasting than that of A-fibers. We found that the inhibitory component induced by C-fibers was markedly attenuated by the two opioid peptides mentioned above, but was resistant to pentobarbital. On the contrary, the component mediated by A-fibers was suppressed by pentobarbital but was relatively resistant to the opioid peptides. Thus, the rabbits aortic nerve-renal sympathetic reflex consists of the following 3 subsystems characterized by different physiological and pharmacological properties: sympatho-inhibitory systems activated by barosensory A- or C-fibers and a sympatho-excitatory system attributable to C-fibers probably of nociceptive modality.

Two Types of Hypotensive Effect of Beta-Blocking Agents

In anesthetized and immobilized rats, an hour-long continuous intravenous injection of dl-propranolol (PR; 3 mg/kg), pindolol (PI; 1 mg/kg), oxprenolol (OX; 3 mg/kg) or atenolol (AT; 3 mg/kg) invariably resulted in moderate hypotension. When the drug-induced hypotension was plotted against the control arterial pressure (AP), two types of correlation were found. The hypotension induced by PR or PI, both known to accumulate in the brain at a high concentration was positively correlated to the control AP, whereas the hypotension produced by OX or AT, both known to penetrate the blood-brain-barrier poorly, was not. To test the hypothesis that the observed difference was attributable to the presence or lack of sympathoinhibitory action of the drug, the effect of these agents on the renal nerve activity (RNA) was examined. PR or PI diminished the tonic and reflexly evoked RNA, when the evoked RNA was elicited by sciatic nerve stimulation. No such changes were induced by OX or AT. These results demonstrate a modulatory role of sympathoinhibitory effect of beta-blocking agents in their hypotensive action.