[The effects of ketanserin on vascular eicosanoid system in spontaneously hypertensive rats and their implications].
We designed experiments to reveal the effects of a S2 serotonergic receptor antagonist, ketanserin, on the vascular eicosanoid system and the relevance to medial hyperplasia in spontaneously hypertensive rats (SHR). 2-week ketanserin treatment (5 mg/kg/day) significantly decreased systolic blood pressure by 7% when compared to untreated SHR. The blood pressure reduction was associated with a significant decrease in vascular thromboxane A2 (TXA2) generation and sustained prostacyclin (PGI2) production, thereby shifting PGI2/TXA2 ratio toward vasodilatation. In contrast, the trichlormethiazide treatment, which achieved blood pressure reduction to almost the same extent, significantly decreased PGI2/TXA2 ratio. Vasodilator eicosanoids, e. g. PGI2, PGE2 and PGD2, dose-dependently decreased (3H)-thymidine uptake by vascular smooth muscle cells in culture whereas vasoconstrictor TXA2 enhanced (3H) thymidine uptake in a dose dependent manner. Indeed 2 x 10(-5) M ketanserin significantly decreased (3H) thymidine uptake by vascular smooth muscle cells by 48% although the same dose of methysergide, nonspecific serotonin inhibitor, did not affect the uptake by vascular smooth muscle cells. These results clearly indicate that the blood pressure reduction in ketanserin treatment is uniquely associated with a decrease in vascular thromboxane generation, and that it is possibly beneficial to protect vascular wall against medial hyperplasia of vascular smooth muscle cells, an integral component of arterial sclerotic changes in hypertension.
Uehara
Y
Y
Numabe
A
A
Hirawa
N
N
Ishimitsu
T
T
Takada
S
S
Matsuoka
H
H
Yagi
S
S
Sugimoto
T
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D007650:Ketanserin / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis* / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013931:Thromboxanes / Q000096:biosynthesis* / Q000502:physiology
D011453:Prostaglandins; D013931:Thromboxanes; D007650:Ketanserin