Regional hemodynamic effects of candesartan cilexetil (TCV-116), an angiotensin II AT1-receptor antagonist, in conscious spontaneously hypertensive rats.
The regional hemodynamic effects of candesartan cilexetil (TCV-116), a selective angiotensin II AT1-receptor antagonist, and enalapril, an angiotensin-converting enzyme inhibitor, were compared in conscious spontaneously hypertensive rats (SHR). A 7-day repeated administration study was carried out. TCV-116 (1 mg/kg, p.o.) and enalapril (10 mg/kg, p.o.) reduced blood pressure to the same extent 5 hr after administration on the 1st and the 7th day. At these points, the cardiac index and organ or tissue blood flow were measured by the non-radioactive colored dye-extraction microsphere technique. Repeated administration of TCV-116, and single and repeated administration of enalapril significantly increased renal blood flow without any changes in the cardiac index. TCV-116 and enalapril also tended to increase splanchnic blood flow following the 1st dose but not the 7th dose. No significant changes in blood flow were observed in the brain, heart, adrenal, skin and skeletal muscle. These results suggest that the antihypertensive effects of TCV-116 and enalapril are attributable to the systemic reduction of vascular resistance caused by the dilatation of blood vessels. These hemodynamic effects of TCV-116, like those of enalapril, may be beneficial in the treatment of hypertension.
Kanagawa
R
R
Pharmaceutical Research Laboratories II, Takeda Chemical Industries, Ltd., Osaka, Japan.
Wada
T
T
Sanada
T
T
Ojima
M
M
Inada
Y
Y
D000284:Administration, Oral; D000311:Adrenal Glands / Q000098:blood supply / Q000187:drug effects; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008863:Microspheres; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000187:drug effects; D013153:Splanchnic Nerves / Q000098:blood supply / Q000187:drug effects; D013777:Tetrazoles; D014655:Vascular Resistance / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D004656:Enalapril; C077793:candesartan cilexetil