Maternal separation (MS) increases acute and chronic norepinephrine (NE) sensitivity revealing sympatho‐activation

Abstract

We reported that MS, a model of early life stress (ELS), induces a greater drop in blood pressure in response to a ganglion blockade and a reduction in the renal filtration capacity that was normalized by renal denervation. We hypothesized that MS sensitizes the peripheral sympathetic system. The aims of this study were to evaluate 1) NE content in vasculature, kidney, spleen, and adrenal tissues, and 2) vascular tone in response to adrenergic agonists from 12 week old MS and control WKY rats. MS consisted of separating half of the male pups from the dam 3 hr a day from days 2–14 of life. NE was unchanged in plasma, thoracic and abdominal aorta while NE content was significantly increased in renal cortex (331±26 vs. 219±38 ng/g tissue), spleen (473±66 vs. 253±28 ng/g tissue) and adrenal gland (1152±189 vs. 303±99 vs. ng/g tissue) from MS vs. control rats (p<0.05). Rats were injected with NE (2 μg/kg, i.p.) and blood pressure monitored by telemetry. Mean arterial pressure was exacerbated in MS vs. control rats (178±1 vs. 147±10 mmHg, p<0.05) within 15 minutes. In a separate group of anesthetized rats, reduction in renal blood flow in response to phenylephrine was attenuated in MS rats compared to control rats (−1.8±0.2 vs. −2.8±0.2 Δml/min, p<0.05, 100 ug/kg), suggesting an adrenergic desensitization. Thus, ELS sensitizes the sympathetic system impairing the normal acute and chronic vascular tone regulation.