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This Article Full Text Full Text (PDF) All Versions of this Article: 293/6/R2260    most recent 00509.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Augustyniak, R. A. Articles by Rossi, N. F. Search for Related Content PubMed PubMed Citation Articles by Augustyniak, R. A. Articles by Rossi, N. F.

NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Acute angiotensin-converting enzyme inhibition evokes bradykinin-induced sympathetic activation in diabetic rats

¹Departments of Medicine and ²Physiology, Wayne State University; and ³John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan

Submitted 13 July 2007 ; accepted in final form 20 September 2007

We have previously shown that acute intravenous injection of the angiotensin-converting enzyme (ACE) inhibitor enalapril in diabetic rats evokes a baroreflex-independent sympathoexcitatory effect that does not occur with angiotensin receptor blockade alone. As ACE inhibition also blocks bradykinin degradation, we sought to determine whether bradykinin mediated this effect. Experiments were performed in conscious male Sprague-Dawley rats, chronically instrumented to measure mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA), 2 wk after streptozotocin (55 mg/kg iv, diabetic, n = 11) or citrate vehicle (normal, n = 10). Enalapril (2.5 mg/kg iv) decreased MAP in normal rats (–15 ± 3 mmHg), while a smaller response (–4 ± 1 mmHg) occurred in diabetic rats. Despite these different depressor responses to enalapril, HR (+44 ± 8 vs. +26 ± 7 bpm) and RSNA (+90 ± 21 vs +71 ± 8% baseline) increased similarly between the groups (P 0.22 for both). Pretreatment with the bradykinin B₂ receptor antagonist Hoe 140 (10 µg/kg bolus followed by 0.8·µg^–1kg·min^–1 infusion) attenuated the decrease in MAP observed with enalapril in normal rats but had no effect in diabetic rats. Moreover, the normal group had smaller HR and RSNA responses (HR: +13 ± 8 bpm; RSNA: +32 ± 13% baseline) that were abolished in the diabetic group (HR: –4 ± 5 bpm; RSNA: –5 ± 9% baseline; P < 0.05 vs. preenalapril values). Additionally, bradykinin (20 µg/kg iv) evoked a larger, more prolonged sympathoexcitatory effect in diabetic compared with normal rats that was further potentiated after treatment with enalapril. We conclude that enhanced bradykinin signaling mediates the baroreflex-independent sympathoexcitatory effect of enalapril in diabetic rats.

angiotensin II; blood pressure; baroreflex