Abstract |
Effects of KT3-671 on vascular and cardiac sympathetic neurotransmission were investigated in pithed rats. The pressor response to spinal stimulation (5 Hz) of the pithed rat without the adrenals was approximately 75% of that with the adrenals. Guanethidine (8 mg/kg, i.v.) decreased by about 76% the pressor response to sympathetic stimulation in the pithed rat with intact adrenals and the guanethidine-resistant response was almost completely abolished by bilateral adrenalectomy. Therefore, the following experiments were done using the pithed rat without the adrenals. KT3-671 (1-10 mg/kg, i.v.) as well as losartan (1-10 mg/kg, i.v.) inhibited dose-dependently the pressor response to sympathetic stimulation. KT3-671 was approximately four times more potent than losartan in inhibiting the pressor response. The two angiotensin II subtype 1 receptor antagonists (10 mg/kg, i.v.) did not affect the pressor response to exogenously administered norepinephrine. Neither KT3-671 nor losartan influenced the tachycardia induced by spinal stimulation and isoprenaline. Intravenous infusion of angiotensin II (100 ng/kg/min) did not affect both pressor and tachycardic responses to sympathetic stimulation. In conclusion, KT3-671 as well as losartan inhibits vascular but not cardiac sympathetic neurotransmission of the pithed rats, which may contribute to its overall antihypertensive efficacy.
|
Authors | Y Takata, J Kurihara, T Yoda, S Suzuki, Y Matsuoka, Y Okubo, H Kato |
Journal | Journal of cardiovascular pharmacology
(J Cardiovasc Pharmacol)
Vol. 37
Issue 4
Pg. 427-36
(Apr 2001)
ISSN: 0160-2446 [Print] United States |
PMID | 11300656
(Publication Type: Journal Article)
|
Chemical References |
- Angiotensin Receptor Antagonists
- Antihypertensive Agents
- Imidazoles
- KT3 671
- Receptor, Angiotensin, Type 1
- Receptor, Angiotensin, Type 2
- Sympathomimetics
- Tetrazoles
- Angiotensin II
- Propranolol
- Losartan
- Norepinephrine
- Guanethidine
|
Topics |
- Adrenalectomy
- Angiotensin II
(pharmacology)
- Angiotensin Receptor Antagonists
- Animals
- Antihypertensive Agents
(pharmacology)
- Blood Pressure
(drug effects, physiology)
- Decerebrate State
- Electric Stimulation
- Guanethidine
(pharmacology)
- Heart Rate
(drug effects)
- Imidazoles
(pharmacology)
- Losartan
(pharmacology)
- Male
- Norepinephrine
(pharmacology)
- Propranolol
(pharmacology)
- Rats
- Rats, Wistar
- Receptor, Angiotensin, Type 1
- Receptor, Angiotensin, Type 2
- Spinal Cord
(physiology)
- Sympathetic Nervous System
(drug effects, physiology)
- Sympathomimetics
(pharmacology)
- Tetrazoles
(pharmacology)
|