Angiotensin II Type 1 Receptor Activation in the Subfornical Organ Mediates Sodium-induced Pressor Responses In Wistar Rats

Missale Tiruneh, Université D'Ottawa / University Of Ottawa, Université D'Ottawa / University Of Ottawa
2012
Na+ sensitive hypertension in Dahl salt sensitive rats (Dahl S) or spontaneously hypertensive rats (SHR) is linked to intrinsic changes in the brain that favour increased Na+ entry into the cerebrospinal fluid (CSF) followed by increases in sympathetic hyperactivity and hypertension (Huang et al 2004). Similar responses are observed in salt resistant and Wistar rats that receive an intracerebroventricular (icv) infusion of Na+ rich artificial cerebrospinal fluid (aCSF) (Huang et al 2001, 2006).
more » ... et al 2001, 2006). Downstream to increased CSF[Na+], a pathway has been described involving mineralocorticoid receptors (MRs), benzamil sensitive Na+ channels, "ouabain", and angiotensin II type 1 receptors (AT1-R) (Huang et al 1998, Zhao et al 2001, Wang and Leenen 2003, Huang et al 2008). Blood pressure (BP) responses to increased CSF[Na+] may involve activation of AT1-R in the subfornical organ (SFO) as the BP response to injection of NaCl into a lateral ventricle can be blocked by AT1-R blockade in the SFO (Rohmeiss et al 1995a). The role of aldosterone and AT1-R in the SFO was investigated in mediating the BP and heart rate (HR) response to increases in CSF[Na+] and local [Na+]. Results show that infusion of 0.45M and 0.6M Na+ rich aCSF into the SFO increases BP but not HR. The BP is unchanged by infusion of a mannitol solution osmotically equivalent to 0.6M Na+ rich aCSF indicating that the SFO is Na+ sensitive. The BP response to a lower concentration of Na+ (0.45M) is enhanced by prior infusion of aldosterone while BP response to 0.6M is not further enhanced suggesting that the SFO may have maximal responsiveness to acute increases in [Na+] at 0.6M. The BP responses to Na+ rich aCSF in the SFO and the enhancement of those responses by aldosterone can be blocked by infusion of the AT1-R blocker Candesartan in the SFO. This response appears therefore to be mediated in the SFO through AT1-R activation, likely through Ang II release in the SFO. ICV infusion of Na+ rich aCSF increases BP but not HR and this response is partially blocked b [...]
doi:10.20381/ruor-5289 fatcat:tphrlivye5gkvi3hlp7yn7pzsm