Role of ERK and Rho kinase pathways in central pressor action of urotensin II.
BACKGROUND
It has been shown that central urotensin II acts on the central nervous system to increase arterial pressure in conscious rats.


OBJECTIVE
To investigate the intracellular signal transduction mechanisms of the central cardiovascular action of urotensin II.


METHODS
The effects of intracerebroventricular (i.c.v.) administration of the extracellular signal-regulated protein kinase (ERK) inhibitor, PD 98059 (20 nmol), the phosphatidylinositol 3 (PI3) kinase inhibitor, wortmannin (20 nmol), or the Rho kinase inhibitor, Y-27632 (20 nmol), on cardiovascular responses to i.c.v. urotensin II (10 nmol) were determined in conscious rats.


RESULTS
I.c.v. injection of urotensin II increased both arterial pressure and heart rate (14.9 +/-1.5 mmHg and 94.6 +/-12.8 beats/min, respectively; P < 0.05 for each). Pretreatment with PD 98059 or Y-27632 significantly (P < 0.01 and P < 0.05, respectively) attenuated the pressor response induced by i.c.v. urotensin II (6.6 +/-1.4 and 6.9 +/-1.2 mmHg, respectively). Pretreatment with a mixed solution of PD 98059 and Y-27632 failed to cause further suppression of the urotensin II-induced pressor responses (4.5 +/-0.9 mmHg). In contrast, pretreatment with i.c.v. wortmannin failed to influence the pressor response induced by i.c.v. urotensin II (12.6 +/-1.3 mmHg). The tachycardiac response induced by i.c.v. urotensin II was not influenced by pretreatment with PD 98059, Y-27632 or wortmannin.


CONCLUSIONS
These findings suggest that the ERK and Rho kinase pathways, but not the PI3 pathway, may be involved in the central pressor action of urotensin II in conscious rats.
Lin
Yingzi
Y
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
Matsumura
Kiyoshi
K
Tsuchihashi
Takuya
T
Fukuhara
Masayo
M
Fujii
Koji
K
Iida
Mitsuo
M
D000577:Amides / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D003243:Consciousness; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014579:Urotensins / Q000494:pharmacology*; D000077191:Wortmannin; D054460:rho-Associated Kinases
D000577:Amides; D000730:Androstadienes; D004791:Enzyme Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D005419:Flavonoids; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011725:Pyridines; D014579:Urotensins; D000077191:Wortmannin; D054460:rho-Associated Kinases; C108830:Y 27632; C029677:urotensin II; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one