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.
Kimura
Shoji
S
Department of Pharmacology, Research Equipment Center and Radioisotope Research Center, Kagawa University Medical School, Kagawa, Japan.
Zhang
Guo-Xing
GX
Nagai
Yukiko
Y
Miyata
Kayoko
K
Nishiyama
Akira
A
Shokoji
Takatomi
T
Yao
Li
L
Fan
Yu-Yan
YY
Rahman
Matlubur
M
Fujisawa
Yoshihide
Y
Miyatake
Akira
A
Abe
Youichi
Y
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