KT3-671, an angiotensin AT(1) receptor antagonist, attenuates vascular butnot cardiac responses to sympathetic nerve stimulation in pithed rats

Effects of KT3-671 on vascular and cardiac sympathetic neurotransmission we re investigated in pithed rats. The presser 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 presser response to sympathetic stimulation in the pithed rat with intact adrenals and the guanethidine-resistant response was almost completely abol ished 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 pres sor response to sympathetic stimulation. KT3-671 was approximately four tim es more potent than losartan in inhibiting the presser response. The two an giotensin Il subtype 1 receptor antagonists (10 mg/kg, i.v.) did not affect the presser response to exogenously administered norepinephrine. Neither K T3-671 nor losartan influenced the tachycardia induced by spinal stimulatio n and isoprenaline. Intravenous infusion of angiotensin II (100 ng/kg/min) did not affect both presser and tachycardic responses to sympathetic stimul ation. In conclusion, KT3-671 as well as losartan inhibits vascular but not cardiac sympathetic neurotransmission of the pithed rats, which may contri bute to its overall antihypertensive efficacy.