• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.220-225
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• 1993

Effect of BR-900317 on the angiotensin I-induced pressor response in pithed rats and the effects of its single oral administration on plasma angiotensin converting enzyme (ACE) activities in normotensive rats and on the cardiovascular system in hypertensive model rats (SHR, RHR), were compared with those of captopril. BR-900317 attenuated the angiotensin I-induced pressor effects in pithed rats. In a single oral dose administration study, BR-900317 inhibited the plasma ACE activities in a dose-dependent fashion. Duration of the action of BR-900317 was similar to that of captopril. BR-900317 produced antihypertensive effect in spontaneously hypertensive rats and dose-dependent antihypertensive effect in 2-kidney Goldblatt hypertensive rats without affecting heart rate. These results suggest that the main mechanism of the antihypertensive effect of BR-900317 is the suppression of angiotensin II production due to the inhibition of the ACE.

• The Korean Journal of Pharmacology
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• v.27 no.1
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• pp.21-31
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• 1991

When administered intracerebroventricularly (icv), cholinergic nicotinic agents, nicotine and DMPP, as well as cholinergic muscarinic agents, muscarine and bethanechol, produced pressor responses in urethane-anesthetized vagotomized rabbits. The response patterns to nicotine and to DMPP were similar, while the bethanechol response resembled the muscarine pattern. The pressor response to nicotine and DMPP was markedly inhibited by icv mecamylamine but not by icv pirenzepine, whereas the response to muscarine and bethanechol was inhibited by icv pirenzepine but not by icv mecamylamine, suggesting that both nicotinic and muscarinic receptors in the brain are involved in the action. Intravenous pretreatments of animals with regitine, reserpine, enalapril, saralasin, both regitine and enalapril, both regitine and saralasin, SK&F-100273 did not prevent the pressor response to nicotine and muscarine. Iv pretreatments with both regitine and SK&F-100273 inhibited the nicotine response without affecting the muscarine response, whereas pretreatments with three agents, regitine, enalapril and SK&F-100273, inhibited the muscarine response. The nicotine-induced elevated blood pressure as well as the muscarine-induced were lowered by regitine but not by enalapril or by SK&F-100273. Enalapril was without effect on the nicotine hypertension in rabbits treated with regitine or both regitine and SK&F-100273, whereas SK&F-100273 lowered the nicotine hypertension in regitine-treated animals. Enalapril did not enhance the lowering effect of SK&F-100273 in regitine-treated ones, nor did it cause a fall of the muscarine hypertension induced in regitine-treated rabbits, but it did lower the blood pressure in animals treated with both regitine and SK&F-100273. Likewise, SK&F-100273 did not cause a fall of the muscarine hypertension induced in regitine-treated rabbits, but it did lower the blood pressure in animals treated with both regitine and enalapril. These data suggest that the nicotine-induced hypertensive state is related to at least two systems in the periphery-sympathetic and vasopressin, whereas in the muscarine-induced hypertensive state three systems in the periphery are involved, i.e., the sympathetic, vasopressin and angiotensin system. The hypotensive effect of regitine on basal arterial blood pressure levels of rabbits was not influenced by pretreatment with either of enalapril or SK&F-100273, but significantly potentiated by treating with both enalapril and SK&F-100273, suggesting participation of the sympathetic and the renin-angiotensin system as well as the vasopressin system in maintenance of arterial blood pressure.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.10 no.11
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• pp.3473-3479
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• 2009

The pharmacological profile of KR-31081, a newly synthesized AT1 receptor antagonist, was evaluated in pithed rats, conscious renal hypertensive rats (RHRs) and conscious furosemide-treated beagle dogs. In pithed rats, KR-31081 (i.v.) induced a non-parallel right shift in the dose-pressor response curve to angiotensin II (ID50: 0.05 mg/kg) with a dose-dependent reduction in the maximum responses; this antagonistic effect was about 40 times more potent than losartan (ID50: 1.74 mg/kg) which showed competitive antagonism. KR-31081 did not alter the responses induced by other agonists such as norepinephrine and vasopressin. In RHRs, orally given KR-31081 produced a dose-dependent and long-lasting (>24 h) antihypertensive effect with a higher potency to losartan (ED20: 0.30 and 3.36 mg/kg, respectively). In furosemide-treated dogs, orally given KR-31081 produced a dose-dependent and long-lasting (>8h) antihypertensive effect with a rapid onset of action (time to Emax: 1-1.5 h) and 20-fold greater potency than losartan (ED20: 0.41 and 8.13 mg/kg, respectively). These results suggest that KR-31081 is a potent, orally active AT1 receptor antagonist useful for the research and diagnostic tools as an added exploratory potential.