Sympathetic and angiotensin-dependent hypertension during cage-switch stress in mice

Abstract

Lee, Dexter L., R. Clinton Webb, and Michael W. Brands. Sympathetic and angiotensin-dependent hypertension during cageswitch stress in mice. Am J Physiol Regul Integr Comp Physiol 287: R1394 -R1398, 2004. First published August 12, 2004 doi:10.1152/ ajpregu.00306.2004.-The goal of this study was to determine the dependence of the acute hypertensive response to a novel model of acute psychosocial stress on the sympathetic and renin-angiotensin systems. Baseline mean arterial pressure (MAP), heart rate (HR), and locomotor activity were measured with telemetry in mice for a 1-h period and averaged 98 Ϯ 1 mmHg, 505 Ϯ 3 beats/min, and 5 Ϯ 1 counts, respectively. Stress was induced by placing a mouse into a cage previously occupied by a different male mouse, and this increased MAP, HR, and activity in the control group by 40 Ϯ 2 mmHg, 204 Ϯ 25 beats/min, and 68 Ϯ 6 counts, respectively. Each variable gradually returned to baseline levels by 90 min after beginning cage switch. Pretreatment with terazosin (10 mg/kg ip) significantly reduced the initial increase in MAP to 12 Ϯ 6 mmHg, whereas MAP for the last 45 min was superimposable on control values. Atenolol (10 mg/ml drinking water) had no effect to blunt the initial increase in MAP but had a growing effect from 10 min onward, decreasing MAP all the way to baseline by 60 min after starting cage switch. Captopril (2 mg/ml drinking water) treatment caused a very similar response. All three treatments significantly decreased the area under the blood pressure curve, and the blood pressure effect could not be attributed uniformly to effects on HR or activity. These data suggest that our novel model of psychosocial stress causes an initial ␣1-receptordependent increase in MAP. The later phase of the pressor response is blocked similarly by a ␤1-receptor antagonist and an ACE inhibitor, independent of HR, suggesting that the ␤1-dependent blood pressure effect is due, in large part, to the renin-angiotensin system. mean arterial pressure; sympathetic nervous system; renin-angiotensin system PSYCHOSOCIAL STRESS INCREASES arterial pressure and also has been linked to chronic renal and cardiovascular disease, including hypertension (1,9,17,19). Stress causes activation of the sympathetic nervous system (SNS) and the hypothalamicpituitary-adrenocortical axis, with responses that include increases in body temperature, blood pressure, heart rate (HR), and plasma glucocorticoid concentration. Interference with either system compromises the body's ability to respond to the stressors (2,16,20). The well-described effects of the SNS are mediated through ␣-and ␤-adrenergic receptors located on the heart and throughout the vascular system, which includes the stimulation of renin secretion and subsequent increase in ANG II production (3,4,7,8,10,18).We have a new experimental model of psychosocial stress that is caused by placing a male mouse in a cage previously occupied by another male mouse. Termed cage switch (CS), this is a modification of earlier models of stress, in which rats ...

Acute Pressor Response to Psychosocial Stress Is Dependent on Endothelium‐Derived Endothelin‐1

“…Baseline mean arterial pressure during the 3 hours before CSS did not differ between genotypes (flox versus VEETKO, 106.4±2.0 versus 100.2±2.7 mm Hg; P =0.099; flox, n=7; VEETKO, n=9). CSS induced a rapid increase in systolic, diastolic, and mean arterial pressures in flox mice, with a maximum increase of ≈40 mm Hg, a magnitude consistent with previously published reports in control mice 3, 25. In contrast, the pressor response in the 10 minutes following CSS was significantly blunted in VEETKO mice (Figure 1A through 1C).…”

“…In the present study, we demonstrate that VEETKO mice exhibit blunting of the rapid increase in blood pressure in the first 10 minutes of the response to CSS and that the genotype difference in the pressor response diminishes with increasing time past the initiation of the stressor. These findings demonstrate that endothelium‐derived ET‐1 contributes to the early pressor response to CSS in mice, a contribution that is temporally similar to the contribution of α 1 ‐adrenergic receptors 3. Therefore, we sought to determine if there is a difference in α 1 ‐adrenergic sensitivity in conduit and resistance arteries from flox and VEETKO mice.…”

“…Specifically, adrenergic receptors play a critical role in mediating the pressor response to CSS, in which α 1 ‐adrenergic receptors contribute to the abrupt early increase in blood pressure and β 1 ‐adrenergic receptors contribute to the sustained, but not immediate, response 3. In the present study, we demonstrate that VEETKO mice exhibit blunting of the rapid increase in blood pressure in the first 10 minutes of the response to CSS and that the genotype difference in the pressor response diminishes with increasing time past the initiation of the stressor.…”

“…The acute experience of psychosocial stress induces a profound physiological reaction, leading to a rapid increase in blood pressure 1, 2, 3. Acute stress responses are thought to prepare the body for action in life‐threatening situations 4.…”

“…We hypothesized that psychosocial stress‐induced ET‐1 contributes to the rapid increase in blood pressure via activation of the endothelin A (ET A ) receptor and is derived from the endothelium. To test this hypothesis, we conducted experiments using vascular endothelium‐specific ET ‐1 knockout mice (VEETKO) and control mice that were homozygous for the floxed allele (flox) male mice exposed to cage switch stress (CSS), an established experimental model of acute psychosocial stress 3, 25…”