Ganglionic action of angiotensin contributes to sympathetic activity in renin-angiotensinogen transgenic mice.
In addition to central nervous system actions, angiotensin (Ang) II may increase sympathetic nerve activity (SNA) via a direct action on sympathetic ganglia. We hypothesized that sympathetic ganglionic actions of endogenous Ang II contribute to SNA in transgenic mice that overexpress renin and angiotensinogen (R+A+ mice). Renal SNA and arterial pressure were recorded in anesthetized R+A+ and littermate control mice before and after ganglionic blockade, and after additional blockade of angiotensin type 1 (AT1) receptors with losartan. Ganglionic blockade essentially abolished SNA in control mice, but only reduced SNA to 47+/-18% of baseline in R+A+ mice. The residual SNA remaining after ganglionic blockade in R+A+ mice was reduced from 47+/-18% to 8+/-6% of baseline by losartan (P<0.05). The sympathoinhibitory response to losartan was accompanied by an enhanced decrease in arterial pressure in R+A+ mice compared with that observed in control mice. AT1 receptor expression in sympathetic ganglia, as measured by real-time reverse transcription-polymerase chain reaction, was increased approximately 3-fold in R+A+ versus control mice. The results demonstrate that, as anticipated, essentially all of the renal postganglionic SNA in control mice is driven by preganglionic input. The major new finding is that Ang II-evoked ganglionic activity accounts for approximately 40% of total SNA in R+A+ mice. The significant contribution of the direct ganglionic action of Ang II in R+A+ mice likely reflects both increased levels of Ang II and upregulation of AT1 receptors in sympathetic ganglia.
Ma
Xiuying
X
Cardiovascular Center and Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
Sigmund
Curt D
CD
Hingtgen
Shawn D
SD
Tian
Xin
X
Davisson
Robin L
RL
Abboud
Francois M
FM
Chapleau
Mark W
MW
D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers; D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002714:Chlorisondamine / Q000494:pharmacology; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000503:physiopathology*; D005730:Ganglionic Blockers / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation; D019808:Losartan / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D012083:Renin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000503:physiopathology
D047228:Angiotensin II Type 1 Receptor Blockers; D005730:Ganglionic Blockers; D000808:Angiotensinogen; D000804:Angiotensin II; D012083:Renin; D002714:Chlorisondamine; D019808:Losartan