Astroglia are a possible cellular substrate of angiotensin(1-7) effects in the rostral ventrolateral medulla.
OBJECTIVE
Angiotensin(1-7) (Ang1-7) acting at the level of the rostral ventrolateral medulla (RVLM) affects arterial pressure. The cellular substrate of Ang1-7 remains unknown. We sought to determine which cell types in RVLM could mediate its actions and whether these are altered in the spontaneously hypertensive rat (SHR).


RESULTS
Astrocytes, catecholaminergic (CA-ergic) and non-CA-ergic neurones were targeted with adenoviral vectors in organotypic slice cultures from Wistar rats and SHR. Astrocytic Ca(2+) signalling was monitored using a genetically engineered Ca(2+) sensor Case12. CA-ergic neurones expressed enhanced green fluorescent protein (EGFP) under control of the PRS x 8 promoter, whereas non-CA-neurones expressed EGFP under control of the synapsin-1 promoter. Neurones were recorded in whole cell mode while [Ca(2+)](i) was monitored using Rhod-2. RVLM astrocytes responded to Ang1-7 (200-1000 nM) with concentration-dependent [Ca(2+)](i) elevation. In SHR, the response to 1000 nM was significantly attenuated. The competitive Ang1-7 receptor antagonist A779, but not the AT(1) receptor blocker (losartan), suppressed Ang1-7-induced [Ca(2+)](i) elevations, which were also antagonized by blocking intracellular Ca(2+) stores. Ang1-7 evoked no consistent changes in [Ca(2+)](i) or membrane excitability in CA-ergic or non-CA-ergic neurones in either rat strain.


CONCLUSIONS
Astroglia are a plausible cellular target of Ang1-7 in RVLM. Our data suggest that astrocytic responsiveness to Ang1-7 is reduced in SHR. We hypothesise that Ang1-7 modulates astrocytic signalling which in vivo may affect local metabolism and microcirculation, resulting in changes in activity of RVLM pre-sympathetic neurones and hence blood pressure.
Guo
Fang
F
Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China.
Liu
Beihui
B
Tang
Feige
F
Lane
Samantha
S
Souslova
Ekaterina A
EA
Chudakov
Dmitriy M
DM
Paton
Julian F R
JF
Kasparov
Sergey
S
D000803:Angiotensin I; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015374:Biosensing Techniques; D001794:Blood Pressure / Q000187:drug effects; D020013:Calcium Signaling; D002395:Catecholamines / Q000378:metabolism; D004195:Disease Models, Animal; D017930:Genes, Reporter; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008564:Membrane Potentials; D018613:Microscopy, Confocal; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D046509:Tissue Culture Techniques
C092006:7-Ala-angiotensin (1-7); D047228:Angiotensin II Type 1 Receptor Blockers; D002395:Catecholamines; D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7); D019808:Losartan