Direct interaction between the sympathetic and renin-angiotensin system inmyocardial tissue: a microdialysis study in anaesthetised rats

It has been suggested that local activation of the renin-angiotensin system is involved in early stages of myocardial pathophysiology. To date, there is increasing evidence for interactions between the renin-angiotensin syste m and the sympathetic nervous system; consequently, local sympathetic activ ation may also be involved in this. Microdialysis has great potential in th e direct investigation of neurohormonal interactions. Therefore, the presen t study employs microdialysis to study the local effects of exogenous angio tensin II on the interstitial norepinephrine concentration of the normally innervated left ventricle of the anaesthetised rat. The present study inves tigates the effect of increasing dosages of exogenous angiotensin II on loc al interstitial norepinephrine. Furthermore, a single dose of losartan was infused on top of the highest dose of angiotensin II, in order to study pos sible involvement of angiotensin II type 1 (AT(1)) receptors. Both infusion and sampling were carried out locally, via the microdialysis probes. Conco mitantly, circulating norepinephrine levels, heart rate and respiratory rat e were monitored to evaluate physiologic stability of the preparation throu ghout the experiment. Time controls consisted of rats that were perfused wi th only a Ringer's solution. Angiotensin II induced a dose dependent increa se in norepinephrine that was significantly reduced by losartan. Norepineph rine levels in both plasma (infusion experiment and time controls) and the left ventricular wall (time controls) remained stable throughout the experi ment, just as heart rate and respiratory rate did. This study for the first time employs microdialysis to demonstrate direct interaction between the s ympathetic nervous system and the renin-angiotensin system in the rat left ventricle. The data strongly suggest that AT, receptors are involved in thi s interaction, since selective AT(1) receptor blockade with losartan signif icantly reduced the angiotensin II induced norepinephrine concentration. (C ) 2000 Elsevier Science B.V. All rights reserved.