Time-dependent transition of tempol-sensitive reduction of blood pressure in angiotensin II-induced hypertension.
OBJECTIVE
Reactive oxygen species (ROS) participate in the intracellular signalling of angiotensin II. However, the mechanisms of the interaction of ROS with hypertension and mitogen-activated protein kinase (MAPK) in vivo have remained unclear. Angiotensin II infusion provokes sustained hypertension accompanied with enhancement of ROS production; initially hypertension is non-sensitive to ROS, but thereafter becomes sensitive. We examined the time-dependent transition of ROS-sensitive vasoconstriction during angiotensin II infusion and also ROS sensitivity to cardiovascular MAPK activation in acutely and chronically angiotensin II-infused rats.


RESULTS
During infusion of a pressor dose of angiotensin II to conscious Sprague-Dawley rats, tempol, a superoxide dismutase mimetic, was administered at 10 min, some 1, 3, 6, 12 and 24 h after the start of infusion. The magnitude of the reduction in blood pressure by tempol was initially negligible, but gradually enlarged, and reached a maximum of 96% of delta increase by angiotensin II at 12 h. However, even after sensitization to tempol, superimposed angiotensin II enabled an increase of blood pressure under tempol treatment. In chronically angiotensin II-infused rats, superimposed angiotensin II exhibited tempol quenchable MAPK activation.


CONCLUSIONS
These results indicate that the mechanisms of angiotensin II-induced vasoconstriction may shift from being non-sensitive to ROS to sensitive within 12 h; nevertheless, both ROS non-sensitive vasoconstriction and ROS-sensitive MAPK activation by angiotensin II, which are both seen in the acute phase of infusion, are restored in the late maintaining phase of prolonged angiotensin II infusion.
Department of Pharmacology, Research Equipment Center and Radioisotope Research Center, Kagawa University Medical School, Kagawa, Japan.
Shoji
S
Kimura
Guo-Xing
GX
Zhang
Yukiko
Y
Nagai
Kayoko
K
Miyata
Akira
A
Nishiyama
Takatomi
T
Shokoji
Li
L
Yao
Yu-Yan
YY
Fan
Matlubur
M
Rahman
Yoshihide
Y
Fujisawa
Akira
A
Miyatake
Youichi
Y
Abe
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D006321:Heart / Q000502:physiology; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019255:NADPH Oxidases / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000975:Antioxidants; D003497:Cyclic N-Oxides; D012333:RNA, Messenger; D013113:Spin Labels; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D019255:NADPH Oxidases; D020928:Mitogen-Activated Protein Kinases; C001803:tempol