Altered regulation of endothelin A receptor subtype in the cerebral arterioles in response to a Japanese-style diet, in stroke-prone hypertensive rats.
OBJECTIVE
To investigate the expression of endothelin (ET)-1 and its receptors in the cerebral arterioles of stroke-prone (spSHR) and control spontaneously hypertensive rats (SHRs) and the changes in endothelin receptor subtypes A and B density elicited by a stroke-permissive diet, before the development of stroke.


METHODS
Six-week-old SHRs (n=11) and spSHRs (n=11) were assigned to either a regular or a "Japanese"-style diet, in addition to 1% NaCl in the drinking water, for 4 weeks. Cryosections (10 microm thick) of rat brain were assessed for endothelin receptor distribution and density by autoradiography with [125I]ET-1 (10(-10) mol/l) in the presence of cold ET-1 (10(-6) mol/l) or the peptide antagonists BQ-123 (10(-6) mol/l) or BQ-788 (10(-6) mol/l). Reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry were used to detect specific mRNAs and localize immunoreactive ET-1 and ET(A) and ET(B).


RESULTS
In both strains, immunoreactive ET-1 was detected in the endothelium of cerebral arterioles, and RT-PCR and autoradiography demonstrated the coexistence of both receptor subtypes in brain homogenates and the cerebral arteriole walls, respectively. With the regular diet, the ET(A) receptor density was lower in SHRs than in spSHRs (P = 0.007), whereas the ET(B) receptor density was similar (P = NS). The Japanese-style diet increased the density of ET(A) receptors (P = 0.006) in SHRs, but decreased it (P = 0.019) in spSHRs. No effect was seen on ET(B) receptor density.


CONCLUSIONS
ET(A) and ET(B) receptor subtypes are expressed in the wall of cerebral arterioles of SHRs and spSHRs. The latter strain showed a marked increase in ET(A) receptor density under a regular diet, in addition to an altered regulation in response to a stroke-permissive diet.
Rossi
Gian Paolo
GP
Department of Clinical and Experimental Medicine, Clinica Medica 4, University Hospital, University of Padua, via Giustiniani 2, 35126 Padua, Italy. gianpaolo.rossi@unipd.it
Colonna
Stefania
S
Belloni
Anna S
AS
Savoia
Carmine
C
Albertin
Giovanna
G
Nussdorfer
Gastone G
GG
Hagiwara
Hiromi
H
Rubattu
Speranza
S
Volpe
Massimo
M
D000818:Animals; D001160:Arterioles / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002560:Cerebrovascular Circulation; D004032:Diet; D019332:Endothelin-1 / Q000378:metabolism; D016232:Endothelins / Q000235:genetics; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007564:Japan; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000235:genetics / Q000378:metabolism*; D020521:Stroke / Q000235:genetics
D019332:Endothelin-1; D016232:Endothelins; D020033:Protein Isoforms; D011498:Protein Precursors; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin