Adolescent vulnerability to cardiovascular consequences of chronic social stress: Immediate and long‐term effects of social isolation during adolescence

Abstract

It has been demonstrated that disruption of social bonds and perceived isolation (loneliness) are associated with an increased risk of cardiovascular morbidity and mortality. Adolescence is proposed as a period of vulnerability to stress. Nevertheless, the impact of chronic social stress during this ontogenic period in cardiovascular function is poorly understood. Therefore, the purpose of this study was to compare the impact in cardiovascular function of social isolation for 3 weeks in adolescent and adult male rats. Also, the long-term effects of social isolation during adolescence were investigated longitudinally. Social isolation reduced body weight in adolescent, but not in adult animals. Disruption of social bonds during adolescence increased arterial pressure without affecting heart rate and pulse pressure (PP). Nevertheless, social isolation in adulthood reduced systolic arterial pressure and increased diastolic arterial pressure, which in turn decreased PP without affecting mean arterial pressure. Cardiovascular changes in adolescents, but not adults, were followed by facilitation of both baroreflex sensitivity and vascular reactivity to the vasodilator agent acetylcholine. Vascular responsiveness to either the vasodilator agent sodium nitroprusside or the vasoconstrictor agent phenylephrine was not affected by social isolation. Except for the changes in body weight and baroreflex sensitivity, all alterations evoked by social isolation during adolescence were reversed in adulthood after moving animals from isolated to collective housing. These findings suggest a vulnerability of adolescents to the effects of chronic social isolation in cardiovascular function. However, results indicate minimal cardiovascular consequences in adulthood of disruption of social bonds during adolescence.

Adolescent vulnerability to cardiovascular consequences of chronic emotional stress: Review and perspectives for future research

“…Indeed, a progressive increase in the number of ␣-adrenoceptor in peripheral tissues (e.g., lung, kidney, and liver) is observed during pre-weaning period, reaching adult values by PND30 to PND50 (McCaughran et al, 1986;Slotkin et al, 1986). These findings are consistent with the data discussed in the next section demonstrating that arterial pressure increases during the pre-weaning period (Bartolome et al, 1980;Kasparov and Paton, 1997), but values are adult-like by PND25 (Canese et al, 2009;Cruz et al, 2016;Duarte et al, 2015a,b;Kasparov and Paton, 1997). In fact, recently, we reported similar sympathetic vasomotor modulation at PND38 and PND70 (Duarte et al, 2015b).…”

“…In fact, recently, we reported similar sympathetic vasomotor modulation at PND38 and PND70 (Duarte et al, 2015b). Additionally, the pressor response to a selective ␣ 1 -adrenoceptor agonist was similar in adolescent and adult animals (Cruz et al, 2016;Duarte et al, 2015a).…”

“…Cardiac baroreflex function does not change during adolescence. For instance, recent results demonstrated similar reflex HR responses to arterial pressure at PND38, PND49, PND60, PND70, and PND81 (Cruz et al, 2016;Duarte et al, 2015a). Analysis of spontaneous baroreflex sensitivity (i.e., evaluation of the baroreflex function over the physiological range of fluctuations in arterial pressure without any pharmacological manipulations) also did not indicate differences in baroreflex function during adolescence (Duarte et al, 2015b).…”

“…Regarding the development of arterial pressure, studies have indicated a progressive increase in arterial pressure values from PND6 to PND8 until between PND20 and PND25 (Bartolome et al, 1980;Kasparov and Paton, 1997). Nevertheless, contrary to HR, arterial pressure evaluated in adolescent animals did not differ from those identified in adulthood (Canese et al, 2009;Cruz et al, 2016;Duarte et al, 2015a,b), thus suggesting that this cardiovascular parameter is completely developed by the weanling.…”

“…Indeed, it has been proposed that some phases of development may be periods of vulnerability to stress (Eiland and Romeo, 2013;McCormick et al, 2010;Spear, 2000). In this regard, results obtained in rodents have indicated adolescence as a developmental period of vulnerability to the effects of stress (Andersen and Teicher, 2008;Cruz et al, 2016;Dahl, 2004;Doremus-Fitzwater et al, 2009;Duarte et al, 2015a;Jankord et al, 2011;Stone and Quartermain, 1997). For instance, reduction in body weight gain, adrenal hypertrophy, and thymic involution induced by chronic stressors are more frequently observed in adolescent than in adult animals (Doremus-Fitzwater et al, 2009;Duarte et al, 2015a;Jankord et al, 2011;Stone and Quartermain, 1997).…”