CHRONIC ACE-INHIBITOR TREATMENT AND ADRENERGIC-MECHANISMS IN SPONTANEOUSLY HYPERTENSIVE RATS

We investigated the effects of chronic treatment with the angiotensin- converting enzyme (ACE) inhibitor fosinopril on cardiac and vascular n oradrenergic neurotransmission as related to cardiovascular hypertroph y in spontaneously hypertensive rats (SHRs). SHRs were treated with fo sinopril at ''high dose'' (SHR_HD, 25 mg/kg/day) or ''low dose'' (SHR_ LD, 1 mg/kg/day) from the 6th to the 12th week of age, and compared to age-matched, untreated SHRs (SHR_C) and Wistar-Kyoto controls (WKY). Blood pressure was significantly reduced in SHR_HD but not in SHR_LD w hen compared to SHR_C. The antihypertensive dose of fosinopril reduced both cardiac and vascular hypertrophy, whereas the low dose was effec tive only in reducing vascular hypertrophy. Several differences in pre synaptic and postsynaptic cardiovascular noradrenergic neurotransmissi on were observed between SHR_C and WKY rats (increased cardiac norepin ephrine concentration, downregulation of cardiac beta-adrenoceptors, r educed alpha-adrenergic receptor-mediated vasoconstrictor response of small mesenteric arteries to exogenous norepinephrine). All these diff erences were abolished by ACE inhibitor treatment, both at antihyperte nsive or at subantihypertensive doses. The results of this study are c onsistent with the hypothesis that chronic ACE inhibition may exert an inhibitory modulation on the peripheral adrenergic transmission, whic h is not related to blood pressure reduction. This modulation does not appear to be a determinant in preventing the development of cardiac h ypertrophy but may play a role in the regression of vascular structura l alterations in spontaneously hypertensive rats.