The role of brain angiotensin II (type 2) receptors and nitric oxide in the renal sympathoinhibitory response to acute volume expansion in conscious rats.
The study was performed to investigate the role of angiotensin II type 2 (AT2) receptors and nitric oxide in the renal sympathoinhibitory response to volume expansion (VEP).



Conscious rats were subjected to volume expansion (VEP) [0.25% body weight/min saline for 10 min intravenously (i.v.)] following intracerebroventricular (i.c.v.) infusion of either saline or angiotensin II (Ang II), or a combination of Ang II with either losartan, PD123319, or N-nitro-L-arginine methyl ester (L-NAME).



Intracerebroventricular losartan, PD123319, or L-NAME did not change baseline mean arterial pressure, heart rate, or renal sympathetic nerve activity (RSNA). However, i.c.v. Ang II increased mean arterial pressure and decreased heart rate and RSNA baselines (113 ± 2 vs. 107 ± 2 mmHg, 365 ± 7 vs. 379 ± 5 beats/min, 1.03 ± 0.13 vs. 1.29 ± 0.15 μV.s, respectively, all P < 0.05). During i.c.v. saline infusion, VEP decreased RSNA by 27 ± 2% (P < 0.05) after 10 min and the magnitude of this response was unchanged during i.c.v. infusion of Ang II, losartan, or PD123319 but was decreased by L-NAME compared with that obtained with i.c.v. saline (14 ± 3 vs. 30 ± 5%, P < 0.05). i.c.v. Ang II in combination with losartan enhanced (41 ± 3 vs. 29 ± 5%) but with PD123319 decreased (15 ± 2 vs. 28 ± 4%, P < 0.05) the renal sympathoinhibition compared with Ang II alone. The renal sympathoinhibitory response was enhanced (43 ± 5 vs. 29 ± 1%, P < 0.05) by i.c.v. infusion of an AT2 agonist, CGP42112 the magnitude of which was unchanged when combined with L-NAME. The sympathoinhibitory response to VEP following Ang II plus L-NAME was similar to Ang II alone.



These findings suggest that activation of central AT2 receptors enhances the renal sympathoinhibitory response to VEP but this effect is not dependent on nitric oxide.
Department of Physiology, Western Gateway Building, University College Cork, College Road, Cork, Ireland.
Mohammed H
MH
Abdulla
Edward J
EJ
Johns
D061605:Administration, Intravenous; D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects*; D001826:Body Fluids / Q000502:physiology; D001921:Brain / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D057967:Infusions, Intraventricular; D007668:Kidney / Q000294:innervation; D019808:Losartan / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D012965:Sodium Chloride / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D004791:Enzyme Inhibitors; D007093:Imidazoles; D009842:Oligopeptides; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C060894:CGP 42112A; C073402:PD 123319; D009569:Nitric Oxide; D012965:Sodium Chloride; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester