Impact of cardiac hypertrophy on arterial and cardiopulmonary baroreflex control of renal sympathetic nerve activity in anaesthetized rats

Abstract

This study aimed to quantify the effect of cardiac hypertrophy induced with isoprenaline and caffeine on reflex regulation of renal sympathetic nerve activity by the arterial and cardiopulmonary baroreceptors. Male Wistar rats, untreated or given water containing caffeine and subcutaneous (s.c.) isoprenaline every 72 h for 2 weeks or thyroxine s.c. for 7 days, were anaesthetized and prepared for measurement of renal sympathetic nerve activity or cardiac indices. Both isoprenaline-caffeine and thyroxine treatment blunted weight gain but increased heart weight and heart weight to body weight ratio by 40 and 14% (both P < 0.01), respectively. In the isoprenaline-caffeine group, the maximal rate of change of left ventricular pressure and the contractility index were higher by 17 and 14% (both P < 0.01), respectively, compared with untreated rats. In the isoprenaline-caffeine-treated rats, baroreflex gain curve sensitivity was depressed by approximately 30% (P < 0/05), while the mid-point blood pressure was lower, by 15% (P < 0/05), and the range of the curve was 60% (P < 0.05) greater than in the untreated rats. An acute intravenous infusion of a saline load decreased renal sympathetic nerve activity by 42% (P < 0.05) in the untreated rats but had no effect in the isoprenaline-caffeine-or the thyroxinetreated groups. The isoprenaline-caffeine treatment induced cardiac hypertrophy with raised cardiac performance and an associated depression in the reflex regulation of renal sympathetic nerve activity by both high-and low-pressure baroreceptors. The thyroxine-induced cardiac hypertrophy also blunted the low-pressure baroreceptor-mediated renal sympatho-inhibition. These findings demonstrate that in cardiac hypertrophy without impaired cardiac function, there is a blunted baroreceptor control of renal sympathetic outflow.

Functional contribution of α1D-adrenoceptors in the renal vasculature of left ventricular hypertrophy induced with isoprenaline and caffeine in Wistar–Kyoto rats

“…LVH was induced with subcutaneous injections of isoprenaline (5.0 mg·(kg body mass) -1 ) on days 1, 4, 7, 10, and 13 of the study, and caffeine was administered orally (62 mg·L -1 in the drinking water, daily for 14 days). This approach is a modification of a previously reported model whereby similar doses of isoprenaline were utilised but only 4 injections were administered (Flanagan et al 2008). The modification in the dosage regimen is based on our preliminary pilot studies.…”

“…This model can be induced experimentally by chronic administration of a combination of isoprenaline and caffeine (Flanagan et al 2008;Buckley and Johns 2011). Caffeine is reported to increase plasma levels of noradrenaline, whereas isoprenaline increases heart rate and work load by stimulating cardiac ␤-adrenoceptors (Graham and Spriet 1995;Kovanecz et al 1997).…”

Impact of l-NAME on the cardiopulmonary reflex in cardiac hypertrophy

“…It is generally recognized that increasing circulatory volume leads to a fall in renal sympathetic nerve activity (RSNA), and vice versa, and has been termed the cardiopulmonary reflex. Interestingly, in two models of cardiac hypertrophy induced by isoprenaline/ caffeine or thyroxine exposure, it was found that the reflex renal sympathoinhibition in response to an acute saline volume load did not occur (4). This implied a deficit in the reflex residing either in the heart or within central pathways.…”

“…*P Ͻ 0.01, compared with innervated kidney. involving 1-wk administration of thyroxine, which has been previously shown to cause a cardiac hypertrophy associated with a blunted renal sympathoinhibitory response to a saline load (4). Importantly, the cardiac hypertrophy enhanced function as cardiac contractility was increased in the isoprenaline/ caffeine model (4).…”

“…involving 1-wk administration of thyroxine, which has been previously shown to cause a cardiac hypertrophy associated with a blunted renal sympathoinhibitory response to a saline load (4). Importantly, the cardiac hypertrophy enhanced function as cardiac contractility was increased in the isoprenaline/ caffeine model (4). The present study has provided further novel insights, in that in the two models of cardiac hypertrophy, the blunted renal sympathoinhibition to the saline load was translated into a functional consequence as the excretory response to the saline load was markedly suppressed in the innervated kidneys, but not in the kidneys subjected to the acute denervation, where they were comparable to those obtained in intact kidneys of normal rats.…”