No abstract

1. The functional role of the paraventricular nucleus (PVN) has been examined by studying its connections with cardiovascular neurons in the medulla and spinal cord and its influence on activity in several sympathetic nerves. 2. Chemical stimulation of neurons within the PVN can elicit pressor responses and can excite reticulo-spinal vasomotor neurons in the rostral ventrolateral medulla (RVLM). 3. The PVN-RVLM excitation is blocked by kynurenic acid applied iontophoretically in the vicinity of RVLM-spinal neurons, suggesting this is a glutamate-dependent pathway. 4. Electrical stimulation of PVN neurons evoked action potentials in RVLM neurons after 27 ms with a small variability. 5. Anterograde and retrograde labelling of PVN and RVLM neurons revealed PVN terminals closely associated with RVLM-spinal neurons and showed that the PVN is connected to the spinal cord via three pathways. 6. Chemical activation of PVN neurons can produce a pattern of activation of cardiovascular neurons similar to that occurring in defence against plasma volume expansion. 7. It is concluded that the PVN connections with the RVLM and spinal cord are important to a role in defending against life-threatening disturbances.

Vasopressin may play an extrahypothalamic role in the central control of the cardiovascular system, specifically acting as a spinal neurotransmitter in the pathway where the paraventricular nucleus (PVN) alters sympathetic outflow. In this study, the effect of stimulating neuronal cell bodies in the PVN on renal sympathetic nerve activity (RSNA) and the possible involvement of vasopressin in the pathway was investigated in anesthetized rats. The PVN was stimulated by microinjection with 0.2 M D,L-homocysteic acid via a glass micropipette, and the hemodynamic and sympathetic responses were recorded. A computerized sympathetic peak-detection algorithm was applied to recordings of sympathetic discharges to retrieve information about the characteristics of RSNA during PVN stimulation. The algorithm scanned the series of RSNA voltages for significant increases followed by significant decreases in a small cluster of voltage values. Once each synchronized RSNA peak had been detected, its corresponding amplitude and peak-to-peak interval were calculated. PVN stimulation consistently increased the amplitude of RSNA (mean 30 +/- 5.6% over control), arterial pressure, and the peak-to-peak interval of discharges. A V1 vasopressin antagonist intrathecally administered as a 500-pmol dose was subsequently able to completely block the hemodynamic response (blood pressure increase of 14 +/- 5%) and a 35 +/- 6% increase in RSNA in response to PVN stimulation and intrathecal vasopressin. Thus spinal vasopressin is likely to be a neurotransmitter involved in the cardiovascular regulation involving the PVN.

Recent evidence is showing that the paraventricular nucleus (PVN) of the hypothalamus plays a key role in autonomic regulation. Studies by the author of the PVN neurones that project to the spinal cord are reviewed. These neurones are inhibited by arterial baroreceptors and excited or inhibited by pulmonary/cardiac vagal afferents. Volume load or low dose atrionatriuretic peptide can stimulate vagal afferents to excite PVN-spinal neurones. Ibotenic acid-induced lesions of PVN-spinal neurones abolish a reflex increase in renal vascular conductance following volume load. This effect appears to be independent of the PVN-vasopressin or oxytocin-containing neurones which directly excite spinal sympathetic neurones. It is suggested that different chemically coded PVN-spinal neurones produce differential effects on spinal cardiovascular neurones, either monosynaptically or via interneurones.

SUMMARY1. The effect of electrical stimulation of the distal cut ends of the renal nerves of unilaterally nephrectomized, anaesthetized cats was studied. Using stimulation parameters of 15 pulses per second (pps), 15 V and 0-2 msec duration, there was an immediate sharp drop in renal blood flow, as determined by an electromagnetic flowmeter, which was maintained for about 2 min. Flow gradually returned to control values over approximately the next 10 min in spite of continued stimulation for up to 30 min.2. Plasma renin activity (PRA) increased markedly after 10 min of stimulation but 20 min later fell towards pre-stimulation values whether stimulation was maintained or not.3. Phentolamine, an az-adrenergic-receptor antagonist, abolished both the blood flow and PRA responses to a 10 min period of renal nerve stimulation.4. When the renal artery was constricted in order to produce blood flow changes similar to those found with renal nerve stimulation, the rise in PRA was similar to that observed with renal stimulation.5. In phentolamine-blocked animals, renal artery constriction, as described, produced the same effect on PRA as was observed with renal nerve stimulation.6. Propranolol, a fl-adrenergic-receptor antagonist, did not block the blood flow response to renal nerve stimulation, but did block the rise in PRA normally associated with renal nerve stimulation.7. It is suggested that the effect of renal nerve stimulation on PRA is mediated, primarily, by changes in renal blood flow and that one of the steps leading to renin release following stimulation is sensitive to propranolol. This step must be distal to the effect on vascular smooth muscle.