INTERACTIONS BETWEEN ANGIOTENSIN-II AND NOREPINEPHRINE ON RENIN RELEASE BY JUXTAGLOMERULAR CELLS

While the interactions between angiotensin II (Ang II) and norepinephr ine (NE) on cardiovascular responses are well known, their effects on renin responses are not. We determined the renin secretion rate (RSR) and intracellular calcium level in juxtaglomerular cells harvested fro m Sprague-Dawley rats using a radioimmunoassay and a two-dimensional c alcium analyzer. The effect of Ang II and NE was inhibitory on RSR and stimulatory on intracellular calcium. The NE-induced RSR response was amplified in the presence of Ang II (20 nmol/l). The NE-induced intra cellular calcium response was also potentiated by the Ang II. There wa s a significant correlation (r = 0.994, p < 0.0001) between the change s in the RSR and those in intracellular calcium levels. Losartan (0.1 mu mol/l), an Ang II type 1 receptor antagonist, blocked the Ang II th reshold RSR responses and completely abolished the Ang II-related enha ncements. The exclusion of calcium from the buffer reduced the maximal RSR response to NE but did not prevent the enhancement, suggesting th e importance of the mobilization of intracellular calcium in the mecha nism. The Ang II-induced RSR was amplified in the presence of NE (0.2 mu mol/l). The Ang II-induced intracellular calcium response was also potentiated by the NE. A significant correlation (r = 0.996, p < 0.000 1) between the changes in the RSR and the changes in intracellular cal cium levels was also noted. Prazosin (1 mu mol/l), an alpha(1)-adrenoc eptor antagonist, blocked the NE threshold RSR responses and abolished the agonist-related enhancements. The calcium-free buffer diminished this amplication with a slight decrease in the maximum RSR response to Ang II. In juxtaglomerular cells, Ang II and NE amplified each other' s RSR responses via an increase in intracellular calcium levels. These responses were mediated by the activation of Ang II type 1 receptors and alpha(1)-adrenoceptors, respectively.