Evidence for descending tonic inhibition specifically affecting sympathetic pathways to the kidney in rats.

1. The present study investigated the possibility that pre- and postganglionic neurones innervating the kidney and spleen in rats are affected by descending inhibitory as well as descending excitatory influences. This hypothesis was tested by comparing the effects of cervical spinal cord transection to the effects of blockade of tonic activity of excitatory neurones in the rostral ventrolateral medulla (RVLM). 2. Electrical discharge of multifibre postganglionic renal and splenic and preganglionic greater splanchnic nerves and 13th thoracic (T13) white rami was recorded in artificially respired, urethane-anaesthetized rats. In one group of rats, descending supraspinal pathways were interrupted by cervical spinal cord transection. In another group, tonic activity of rostral ventrolateral medulla (RVLM) neurones was blocked by bilateral microinjections of the inhibitory amino acid glycine. The effects of spinal cord transection were compared to effects of this bilateral RVLM blockade and to effects of unilateral RVLM blockade described in a previous study. 3. Spinal cord transection caused decreases in preganglionic greater splanchnic and postganglionic splenic nerves which were of the same magnitude as those caused by bilateral blockade of the RVLM. 4. In contrast, discharge of renal nerves was decreased more by bilateral RVLM blockade than by cervical spinal cord transection. Similarly, even unilateral RVLM blockade caused greater decreases in discharge of T13 white rami than were caused by spinal cord transection. 5. These findings suggest that renal nerves and their preganglionic inputs (T13 white rami) are controlled in part by tonic sympathoinhibitory influences which can be unmasked by blockade of the RVLM. These sympathoinhibitory influences do not appear to affect the activity of splanchnic and splenic nerves.

Contribution of the periaqueductal grey matter to the development of hypertension in the spontaneously hypertensive rat.

The dorsomedial periaqueductal grey matter (PAG) of the mid-brain, an important area for organizing the 'defence reaction', was destroyed using radiofrequency lesions in young, pre-hypertensive spontaneously hypertensive rats (SHRs). During the 12 weeks after surgery, systolic blood pressure (SBP) measured by an indirect tail-cuff technique was consistently lower than that of a sham-operated control group of SHRs (final readings of SBP: sham group (n = 6): 239.1 +/- 4.7 mmHg; lesion group (n = 8): 211.1 +/- 8.2 mmHg; P less than 0.05). Subsequent direct measurement of blood pressure in these rats by cannulation of the ventral tail artery indicated that the SBP in both groups was nearly the same (sham group: 204.7 +/- 5.1 mmHg; lesion group: 203.5 +/- 5.1), lying close to the value obtained by the tail-cuff method in the lesion group. Therefore, lesions of the PAG merely prevented the elevation of blood pressure in the SHR caused by the heating and restraint required for indirect measurement of SBP. Furthermore, ablation of the dorsal PAG had no effect on levels of circulating catecholamines, and did not prevent the cardiovascular response to an alerting stimulus (vibration). It is concluded that this region of the brain is not responsible for the development of hypertension in the SHR.

Evaluation of cardiovascular control by neurons in the dorsal medulla of rats.

The contribution of sympathoexcitatory neurons in the dorsal medulla to the regulation of arterial pressure and the involvement of such neurons in integration of physiological responses or in the genesis of basal vasomotor tone are not well defined. In the present study discharge of neurons in the dorsal medulla of anesthetized rats was increased or decreased by microinjections of amino acids to examine effects on systemic arterial pressure, heart rate and blood flow and conductance of the renal and femoral vascular beds. Microinjections of excitatory D, L-homocysteic acid caused increases in arterial pressure of 18 +/- 2 mmHg, increases in heart rate ranging from 5-40 beats/min and renal vasoconstriction; the femoral bed constricted after some injections and dilated in response to others. Injections of the inhibitory amino acid glycine caused no consistent decreases in arterial pressure and heart rate and injections of the gamma-aminobutyric acid analog, muscimol were ineffective. These data demonstrate that neurons in the dorsal region of the rat medulla can contribute to regulation of arterial pressure and can integrate generalized differential changes in regional vascular resistance, but do not appear to be essential for the genesis of basal vasomotor tone.

Cardiac and peripheral vascular contributions to hypotension in spinal cats.

On transection of the cervical spinal cord, substantial decreases in systemic arterial pressure and in discharge of many sympathetic nerves suggest the absence of sympathetic support to the cardiovascular system. However, discharge of mesenteric and splenic nerves is well maintained in spinal cats (R. L. Meckler and L. C. Weaver. J. Physiol. Lond. 396: 139-153, 1988; R. D. Stein and L. C. Weaver. J. Physiol. Lond. 396: 155-172, 1988). We proposed that the low arterial pressure in spinal animals was caused predominantly by decreased cardiac output and vasodilation in muscle and some visceral vascular beds but that sustained mesenteric and splenic discharge was causing significant splanchnic vasoconstriction and partial support of arterial pressure. Therefore, changes in cardiac output, total peripheral resistance, and resistance of constant-flow-perfused mesenteric visceral and hindlimb skeletal muscle vascular beds caused by interruption of cervical spinal pathways were assessed. Blockade of cervical pathways decreased arterial pressure as much by decreasing cardiac output as by decreasing total peripheral resistance. Resistances of the muscle and mesenteric vascular beds decreased equally. In conclusion, hypotension in spinal cats is caused by decreased cardiac output and by vasodilation, which is as prominent in mesenteric as it is in muscle vascular beds. The maintained mesenteric sympathetic discharge in spinal cats appears unable to produce significant support of vascular arterial resistance.

Tonic influences from the rostral medulla affect sympathetic nerves differentially.

Tonically active neurons in the rostral ventrolateral medulla (RVLM) that project to the autonomic regions of the spinal cord are essential for maintenance of arterial blood pressure at normal levels. Microinjection of glycine into the RVLM in anesthetized cats to inhibit the tonic discharge of these neurons caused variable initial responses in renal and mesenteric nerve discharge and arterial blood pressure. These initial responses were consistently followed by more prolonged decreases in renal and mesenteric nerve discharge and decreases in arterial blood pressure. The tonic influences of neurons in the RVLM were found to be distributed unequally to sympathetic nerves because activity of renal nerves was decreased significantly more than that of mesenteric nerves. The variable nerve and cardiovascular responses during the first 1-3 min after glycine injection were not solely due to loading or unloading of baroreceptors because similar initial responses were seen in vagotomized and sinoaortic denervated cats. Additionally, when muscimol was microinjected into the same sites, only consistent and prolonged decreases in nerve discharge and blood pressure occurred. The inhibitory actions of muscimol on RVLM neurons caused significantly greater decreases in renal than mesenteric nerve activity. Together, these findings demonstrate that the tonic discharge of neurons in the RVLM has unequal influences on renal and mesenteric nerves.

Ventrolateral medullary neurones: effects on magnitude and rhythm of discharge of mesenteric and renal nerves in cats.

1. Discharge of whole mesenteric and renal nerves was recorded in eighteen chloralose-anaesthetized, artificially respired cats. 2. Inhibition of tonic activity of neurones within the rostral ventrolateral medulla (RVLM blockade) by bilateral application of glycine caused significant reductions in discharge of renal and mesenteric nerves, arterial blood pressure and heart rate. The decrease in discharge of renal nerves was significantly greater than that of mesenteric nerves. 3. During the response to glycine application, the spinal cord was transected at the first cervical segment. The magnitude of renal nerve discharge after transection was not different from that during blockade of the RVLM. On the other hand, mesenteric nerve activity increased following spinal cord transection, returning to control levels. 4. Power spectral analysis revealed that mesenteric and renal nerves discharged with periodicities ranging from 1 to 6 Hz. Application of glycine to the RVLM reduced the slow rhythm in firing of mesenteric and renal nerves similarly. Transection of the spinal cord resulted in further reduction in the rhythmicity in discharge of both nerves. 5. The results indicate that excitatory drive from the RVLM is crucial for the maintenance of on-going discharge of renal, but not of mesenteric nerves. However, such inputs are apparently essential to maintain the slow rhythm in firing of both nerves.

Vasodilatation in hind-limb skeletal muscle evoked as part of the defence reaction in the rat.

Electrical stimulation of the hypothalamic and mid-brain defence area of the rat's brain elicits a consistent cardiovascular pattern of response of which vasodilatation in the skeletal muscle is an integral component: the mechanisms mediating this vasodilatation were investigated. It is not sensitive to atropine in this species, but it was substantially affected, particularly its later stage (the prolonged tail-end of the response), by either beta-adrenoreceptor antagonists (propranolol, sotalol) or bilateral adrenalectomy. A major part of the hind-limb vasodilatation can therefore be attributed to the action of catecholamines released from the adrenal glands. The initial part of the vasodilatation, which still remained after beta-adrenoreceptor blockade and adrenalectomy, was abolished by intravenous injection of guanethidine and phentolamine and seems therefore due simply to withdrawal of vasoconstrictor tone. In confirmation, stimulation of the sympathetic outflow to the hind-quarters after phentolamine and guanethidine had been used to block vasoconstriction did not reveal a sympathetic vasodilator nerve supply to the hind-limb vasculature.

The hypothalamic and brainstem areas from which the cardiovascular and behavioural components of the defence reaction are elicited in the rat.

Electrical stimulation has been employed to map areas of the rat's brain from which the cardiovascular and behavioural components of the defence reaction are elicited and hence to identify the defence areas in this species. In the anaesthetized rat, the cardiovascular pattern of response includes increases in arterial blood pressure and heart-rate, an atropine-resistant vasodilatation in the hind-limb skeletal muscle, with renal and splanchnic vasoconstriction. This was elicited from comparatively well localized areas, not confined to any particular nuclei. Responses were evoked from the rostro-caudal extent of the hypothalamus but most consistently from a region ventral to the fornix. In the midbrain, responsive sites were localized to the dorsal half of the central grey matter, the tegmentum ventro-lateral to it and a ventro-medial region which continued into the pons. Stimulation using implanted electrodes in conscious rats, within the hypothalamic and midbrain areas described above, elicited typical 'flight' and 'escape' behaviour: thus, the localized regions from which the visceral alerting response is elicited contain neurones or nerve fibres integrating the whole defence-alerting response in the rat, as in other species.

Renal extraction and clearance of p-aminohippurate during saline and dextrose infusion in the rat.

The reliability of the use of p-aminohippurate (PAH) as a clearance marker for the determination of renal plasma flow during saline or dextrose infusion was investigated in conscious and anaesthetized rats. In the conscious rat (wt. 350-400 g) infused for 4 h with 0.85% saline followed by 3 h of 2.5% dextrose, PAH clearance averaged 11.50 +/- 1.45 ml/min during saline infusion and 7.83 +/- 0.82 ml/min during dextrose infusion. The difference was significant (P less than 0.02). Inulin clearance, however, was unchanged. With dextrose as the initial infusate, PAH clearance averaged 5.86 +/- 0.65 ml/min and increased (P less than 0.01) to 8.74 +/- 0.71 ml/min following a change of infusate to saline, although inulin clearance was again unchanged. In separate groups of rats anaesthetized with sodium pentobarbitone, a comparison was made between renal blood flow values calculated from PAH clearance and haematocrit, and those determined simultaneously using an electromagnetic flow probe placed on the left renal artery. During 0.85% saline infusion, the calculated value was 88.1 +/- 8.4% of that measured using the flow probe. During 2.5% dextrose infusion the value determined from PAH clearance was only 47.3 +/- 4.2% of that obtained using the flow probe, and this is significantly (P less than 0.01) lower than the ratio found during saline infusion. In another study, renal venous blood samples were obtained from sodium-pentobarbitone-anaesthetized rats during 0.85% saline or 2.5% dextrose infusions, for calculation of the renal PAH extraction ratio. During saline infusion, PAH extraction averaged 68.3 +/- 2.5%, whereas during dextrose infusion PAH extraction was lower (P less than 0.001) and averaged only 48.8 +/- 3.2%. It is concluded that PAH clearance grossly underestimates renal plasma flow during 2.5% dextrose infusion in the rat.