Key result
Chronic NET blockade with desipramine in rats elevated supine heart rate, reduced sympathetic outflow, and attenuated baroreflex function, modeling severe NET deficiency in orthostatic intolerance.
Why the study?
Does chronic NET blockade with desipramine alter cardiovascular regulation and baroreflex sensitivity in female Sprague-Dawley rats?
Does chronic NET blockade with desipramine alter cardiovascular regulation and baroreflex sensitivity in female Sprague-Dawley rats?
Chronic NET blockade in rats attenuates baroreflex function and reduces sympathetic outflow, providing a mechanistic model for the orthostatic intolerance seen in severe NET deficiency.
NET blockade alters baroreflex sensitivity in rats; leaves open relevance to human orthostatic intolerance.
Orthostatic intolerance is a debilitating syndrome characterized by tachycardia on assumption of upright posture. The norepinephrine (NE) transporter (NET) has been implicated in a genetic form of the disorder. We assessed the combined central and peripheral effects of pharmacological NET blockade on cardiovascular regulation and baroreflex sensitivity in rats. NE reuptake was blocked chronically in female Sprague-Dawley rats by the NET antagonist desipramine (DMI). Treated animals demonstrated an elevated supine heart rate, reduced tyramine responsiveness, and a reduced plasma ratio of the intraneuronal NE metabolite dihydroxyphenylglycol relative to NE, all of which are consistent with observations in human NET deficiency. Spectral analysis revealed a dramatic decrease in low-frequency spectral power after DMI that was consistent with decreased sympathetic outflow. Stimulation of the baroreflex with the vasodilator nitroprusside revealed an attenuated tachycardia in DMI-treated animals. This indicated that the DMI-induced sympathoinhibitory effects of increased NE in the brain stem predominates over the functional elevation of NE stimulation of peripheral targets. Thus attenuated baroreflex function and reduced sympathetic outflow may contribute to the orthostatic intolerance of severe NET deficiency.
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Carson et al. (2002) studied Orthostatic intolerance model. Desipramine (DMI) was evaluated on Cardiovascular regulation and baroreflex sensitivity. Chronic NET blockade with desipramine in rats elevated supine heart rate, reduced sympathetic outflow, and attenuated baroreflex function, modeling severe NET deficiency in orthostatic intolerance.
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