Alterations of Central Vasopressinergic System in Transgenic Rats with Low Brain Angiotensinogen
The consequence of a permanent alteration of the brain renin-angiotensin system (RAS) on central vasopressinergic system was studied at the level of the nucleus tractus solitarii (NTS) of transgenic rats with a deficit in brain angiotensinogen, TGR(ASrAOGEN). Vasopressin (AVP) (100 pmol/ 50nl) or desmopressin (DDAVP, V2 receptor agonist) (100pmol/ 50nl) were microinjected into the NTS of urethane-anesthetized TGR(ASrAOGEN) and Sprague-Dawley (SD) rats. Blood pressure and heart rate were measured via a femoral artery catheter and the baroreflex induced by phenylephrine (baroreflex bradycardia) evaluated. Hypothalamic levels of AVP mRNA were measured by ribonuclease protection assay (RPA). AVP microinjections induced a greater decrease of the MAP in TGR(ASrAOGEN) in comparison with SD rats (-19.9 ± 5.2 vs. -7.5 ± 0.7 mmHg, p<0.05). The significantly higher baroreflex sensitivity observed in TGR compared to that of SD rats was normalized after AVP microinjection (0.76 ± 0.1 vs. 0.3 ± 0.1 ms/ mmHg, before and after AVP microinjection in TGR rats, p<0.05). The microinjections of DDAVP in the NTS produced also a decrease of MAP, which was significantly higher in TGR(ASrAOGEN) in comparison with the control strain (-21.2 ± 0.9 vs. -10 ± 1.2 mmHg, p<0.05). Hypothalamic AVP mRNA levels were not significantly altered in TGR rats. These results demonstrate that a permanent deficit in the brain angiotensinogen synthesis can alter the functionality of central vasopressinergic system. However, the hypothalamic AVP synthesis is not altered. The increased sensitivity to AVP and DDAVP in TGR(ASrAOGEN) rats indicates a functional upregulation of AVP receptors in the NTS and further evidences the interaction between RAS and the vasopressinergic system within the brain. Furthermore, this study for the first time shows the existence of functional DDAVP-sensitive vasopressin receptors at the NTS level.