Continuous intra-arterial administration of a selective endothelin-converting enzyme (ECE) inhibitor CGS 35066 at a dose of 30mg/kg decreased the mean arterial blood pressure (MABP) in conscious unrestrained normotensive rats and spontaneously hypertensive rats (SHRs). At that dose, the magnitude of the antihypertensive effects was greater in SHRs than in normotensive rats. Additional administration of an angiotensin-converting enzyme (ACE) inhibitor benazapril (lotensin) further reduced MABP in normotensive rats and completely blocked hypertension in SHRs. However, when the selective ECE inhibitor was subsequently removed, blood pressure was less inhibited in normotenive rats whereas it remained strongly inhibited in SHRs by the ACE inhibitor alone. These results imply that simultaneous treatment with benazepril and CGS 35066 gave additive antihypertensive effects in normotensive rats but not in SHRs, when both compounds were administered at a dose of 30mg/kg. Our results suggest that: (i) the endothelin (ET) system together with the renin–angiotensin system contribute to the maintenance of blood pressure in normal healthy rats; (ii) while an ECE inhibitor acts as an antihypertensive agent on its own, the sole efficacy of ACE inhibitor at that dose is sufficient to block MABP without the participation of the ET system in SHR.

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