Short-Term Lisinopril Treatment in Old Rats Worsens Impairment of Angiotensin-Induced Reflex Bradycardia

To determine how short-term treatment with an angiotensin-converting enzyme (ACE) inhibitor affects drug-induced reflex bradycardia at different ages in conscious rats, we compared the magnitude of drug-induced reflex bradycardia before and after injecting bolus intravenous doses of lisinopril, 1 mg/100 g, in male Sprague-Dawley rats aged 4 (young) or 19 (old) months. Anesthetic artifacts were avoided by recording all drug-induced cardiovascular responses from femoral arterial cannulas implanted 1 week earlier. For eliciting reflex bradycardia, blood pressure was increased by graded intravenous infusion of angiotensin or phenylephrine. Impairment of reflex bradycardia in old rats occurred only during pressor responses to angiotensin but not when blood pressure was equally increased with phenylephrine. Subsequent administration of lisinopril affected neither pressor and reflex bradycardic responses to phenylephrine nor pressor responses to angiotensin. However, contrary to the baroreflex enhancement described previously by others, the reflex bradycardia induced by angiotensin was reduced by lisinopril treatment but only in old and not in young rats. Thus our results indicate that whereas angiotensin-induced reflex bradycardia was already impaired in old rats before lisinopril was given, it was reduced further after short-term lisinopril treatment.