The Effects of Acute Psychological Stress on Cardiovascular Reactivity and Renal Excretion

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THE EFFECTS OF ACUTE PSYCHOLOGICAL STRESS ON CARDIOVASCULAR REACTIVITY AND RENAL EXCRETION IN A SAMPLE OF NON-SMOKERS

A SSRC Funded Research Study

Matthew C. Scanlin

May 2008

Abstract

A number of studies have reported that activation of the sympathetic nervous system (SNS) by psychological stress can detrimentally affect the cardiovascular and renal systems. When the SNS is activated by psychological stress, the release of catecholamines increase cardiovascular reactivity and stimulate the renin-angiotensin-aldosterone system (RAAS), causing the kidneys to retain sodium and water. These two responses contribute to the observed increases in blood pressure, which can damage organs such as the kidneys and the heart as well as others. Therefore, psychological stress is a contributing risk factor for cardiovascular disease (CVD) and kidney disease. Cardiovascular disease is the number one cause of death in America and kidney disease can be terminal as well. Patients presenting with either condition often have the other or a higher risk of developing it.

The current study assessed the effects of psychological stress on cardiovascular reactivity and renal excretion. Cardiovascular reactivity (HR, SV, CO, SBP, DBP, MAP, & TPR) was measured by bio impedance technology and renal excretion was assessed by urine test strips, graduated cylinders, and hydrometers. Twenty healthy, nonsmoking participants (10 males, 10 females), 19-22 years of age, were assigned randomly to either a stressed condition (n=11) or a non-stressed condition (n=9). Each participant attended two sessions: a pre-testing session consisting of a urine sample collection and questionnaires and a testing session twelve hours later. The testing session measured cardiovascular reactivity and affect (Visual Analog Scale) during a 10-minute baseline period, a 6-minute Paced Auditory Serial Addition Task (PASAT), and a 16-minute recovery period. During the testing session, urine was collected before the start of the baseline period and after the recovery period.

Repeated measures ANOVA revealed significant Task effects for each cardiovascular variable measured (p< .05), such that during the PASAT, HR, CO, SBP, DBP, MAP, & TPR were significantly increased and PEP and SV were significantly decreased as compared to the baseline task. The study also found significant Task x Condition interactions for HR, SBP, DBP, MAP, and PEP (p<. 05), such that participants in the stressed condition demonstrated greater increases in HR, SBP, DBP, & MAP and greater reductions in PEP from baseline to PASAT as compared to participants in the non-stressed condition. No significant Condition effects were found for cardiovascular reactivity. In regards to renal excretion, no main effects for Task or Condition and no Task x Condition effects were found. These findings demonstrate that acute psychological stress affects the cardiovascular system but may not affect the kidneys.

Introduction

Overview

Acute psychological stress can activate the sympathetic nervous system (SNS), causing the release of the catecholamines, epinephrine and norepinephrine (Pike, et al., 1997). These hormones affect the cardiovascular system, by increasing heart rate (HR) and blood pressure (BP). The stimulation of the SNS by acute psychological stress has also been shown to affect the kidneys, as indicated by the increase in plasma levels of renin (Clamage, Vander, & Mouw, 1977). Renin contributes to the renin-angiotensin-aldosterone biochemical pathway, leading to increases in BP due to increases in total peripheral resistance (TPR), the degree of constriction of the smooth muscles in the blood vessels, as well as increased water retention (Givertz, 2001).

The increase in BP, resulting from the effects of SNS stimulation on the cardiovascular and renal systems, can cause damage to organs, the heart and kidneys included. Therefore, it is believed that psychological stress is a risk factor cardiovascular disease (CVD) and kidney disease. Cardiovascular disease is the number one cause of death in the U.S. according to the American Heart Association (AHA, 2003), contributing to the death of one citizen every 35 seconds (Thom et al., 2006). Kidney disease is another large health care concern, afflicting 10.9 million Americans (National Kidney Disease Education Program: Final Strategic Plan, 2001). Given that psychological stress can contribute to the risk for both diseases, it is important to study the effects of acute psychological stress on both the cardiovascular and renal systems. Therefore, before the current study is discussed a brief overview will be provided on psychological stress and the various physiological responses it elicits.

Definition of Psychological Stress

Stress has two prominent working research definitions. Selye has defined stress as a nonspecific response to any emotion or physical stressor (Selye, 1956, 1976, 1982; as cited in Brannon & Feist, 2007). Responses to these stressors involve the nervous, endocrine, and immune systems. The response of the body to a stressor was deemed by Selye the “general adaptation syndrome (GAS).” The Gas was composed of three stages which a person moves through in response to a stressor. The “alarm” stage is the person’s initial reaction to a stressor, where the person physically prepares for the stressor. Then the resistance stage occurs where the person attempts to cope with the stressor. If the person fails to adapt the person may eventually enter the exhaustion stage, where an individual may become ill or die.

Lazarus and Folkman established a definition of psychological stress being a relationship between the person and environment (Lazarus & Folkman, 1984; as cited in Brannon & Feist, 2007). In this relationship psychological stress is mediated by both the cognitive appraisal and coping abilities of an individual. Cognitive appraisal is how threatening the person views the psychological stressor. A person first appraises an event as either stressful or not, then judges the amount of resources available to cope with the event if deemed stressful, and then reappraises the event as stressful or not in light of the available coping resources. Coping is to what extent the person will be able to manage the appraised stressor. Our body has physiological mechanisms in place to help us cope with stressors. When presented with stressors, our body is capable of releasing specific hormones to alter our physiology to better face the stressor. This is commonly referred to as the fight or flight response. Three biological systems are involved in this response, each releasing their own hormones and together they help the body cope with stressors. What follows is a description of the three systems: the renin-angiotensin-aldosterone system (RAAS), the hypothalamic-pituitary-adrenocortical (HPA) system, and the sympathetic adrenal medulla system (SAM).

Stress Response of the Renin-Angiotensin-Aldosterone System (RAAS)

To discuss the stress response of the RAAS, which is initiated by the kidney, it’s essential to first establish the literature’s findings on SNS activity in the kidney. The central nervous system (CNS) is able to communicate with the kidney sympathetically via renal nerves. The kidney is imperative to cardiovascular function, in that it regulates the composition and volume of the body fluids. The kidney responds to signals from mechanosensitive and chemosensitive receptors to maintain homeostasis in body fluids. Not only can the CNS communicate with the kidney, but the kidney has sensory fibers that send signals from sensory receptors on the kidney to the CNS. This acts as feedback system to ensure homeostasis is maintained (Dibona, & Kopp, 1997). It’s important to discuss the physiology of the kidney’s connection to the SNS because when the stress response is discussed it will make reference to the physiology of the kidney and its SNS innervation discussed below.

It has been shown that the renal nerves are important to maintaining homeostasis of the body fluid. A study of nondiuretic rats by Bellow-Reuss, Colindres, Pastoriza-MuÑoz, Mueller, and Gottshalk (1975) found that denervation of the left kidney significantly increased urine volume and sodium excretion in comparison to the innervated right kidney. Thus in the absence of the renal nerves, diuresis and natriuresis occurs, demonstrating the renal nerves involvement in body fluid homeostasis.

To further elaborate upon this finding it’s important to note a study by Wågermark, Ungerstedt, and Ljungqvist (1968) which found that the walls of the juxtaglomerular arterioles, blood vessels that branch off of the kidneys’ arteries, contain granulated cells believed to contain renin and are believed to be directly connected to the SNS. The nerve fibers of these renin containing arterioles are similar to other nerve fibers in the human body which contain norepinephrine, a neurotransmitter of the SNS. Therefore, it can be concluded that this study provides an explanatory mechanism for the release of renin in response to SNS stimulation.

A study demonstrating this mechanism was performed by La Grange, Sloop, and Schmid (1973), who found that stimulation of the renal nerves of dogs resulted in significant decreases in sodium excretion, meaning there was an increase in sodium reabsorption by the kidney. In addition, the study demonstrated that renal nerve stimulation resulted in increased renin production by the kidney (La Grange, Sloop, & Schmid, 1973). Therefore the increased sodium reabsorption could be attributed to the increased renin production which could have activated the renin-angiotensin-aldosterone system (RAAS), producing aldosterone, to induce the sodium reabsorption observed.

Another study by Bunag, Page, and McCubbin (1966) confirmed these findings in the above study. They found that inducing hemorrhage in anesthetized dogs caused the release of renin. This release of renin was prevented by ganglion blockade or local anesthesia in the renal nerves, indicating the involvement of the renal nerves in the release of renin. Furthermore, they observed increases in renin after infusions of norepinephrine, a common SNS neurotransmitter. These two observations, again contribute to the support of renal nerve involvement in the SNS’ release of renin. In addition, stimulation of the renal nerve has been observed to cause increases in norepinephrine in the renal plasma (Bradley, & Hjemdahl, 1984). Norepinephrine, a neurotransmitter and catecholamine affects the function of the kidney by attaching to alpha and beta adrenergic receptors (adrenoceptors) located on multiple parts of the kidney and releasing renin (Winer, Chokshi, Yoon, & Freedman, 1969).

It is important to also note that sympathetic nerve activity is not a global process. It’s believed that most organs are innervated by the SNS and that they are controlled regionally as opposed to globally. For example, when cardiac baroreceptors are activated in the left atrium, they increase cardiac sympathetic nerve activity, but decrease efferent renal nerve sympathetic activity, while leaving other nerves unchanged (Karim, Kidd, Malpus, & Penna, 1972). Thus the SNS doesn’t cause the same systematic changes on all nerves innervating different organs, but rather changes the action of each one independently. So global measures of SNS activity such as plasma norepinephrine, renin, and other hormones or muscle sympathetic nerve activity may not be reliable indicators of regional SNS activity in the kidney. Still these are the most common measures used because they are the most practical measures to attain in studies of stress reactivity.

The stimulation of the SNS as well as renal hypoperfusion, a reduction in blood flow reaching the kidney, and decreased sodium delivery to the kidneys can activate the renin-angiotensin-aldosterone system (RAAS) by releasing renin from the juxtuloglomerular cells, renin-containing cells in the kidney. Renin then cleaves angiotensinogen, an enzyme produced in the liver, giving rise to angiotensin I. Angiotensin I circulates to the lungs, where it is then converted to angiotensin II by angiotensin converting enzyme (ACE). Angiotensin II is important because it continues the RAAS biochemical pathway but it can also independently bind to angiotensin II type 1 and type 2 receptors, leading to sodium and water retention in the kidney and vasoconstriction in the vasculature. Angiotensin II perpetuates the RAAS by being converted to aldosterone in the adrenal cortex. Aldosterone is the final hormone product of the RAAS and it, like angiotensin II, also promotes sodium and water retention in the kidney (Givertz, 2001). Aldosterone production can also result from the release of ACTH (Skowronski, & Feldman, 1994), which is part of the next system discussed below, the hypothalamus-pituitary-adrenal system. The RAAS which begins in the kidney with the release of renin, influences the stress response along with other systems in the body.

Hypothalamus-Pituitary-Adrenal System’s Contribution to the Stress Response

The hypothalamus-pituitary-adrenal (HPA) system is activated by the SNS stimulation and like the RAAS contributes to increases in BP in response but it also increases HR. The hypothalamus is part of the central nervous system and it creates hormones within its neurons and releases them in response to signals sent by other neurons from higher brain centers that respond to environmental signals. The hypothalamus releases corticotrophin-releasing hormone (CRH), which than travels via the blood to the anterior pituitary to produce ACTH which stimulates the adrenal cortex to release cortisol (Hiller-Strumhőfel, & Bartke, 1998) and aldosterone (Skowronski, & Feldman, 1994). Cortisol causes an increase in HR, BP, and glucose metabolism and aldosterone increases BP through the retention of water in the kidney.

Stress Response of the Sympathetic-Adrenal-Medulla (SAM) System

The sympathetic nervous system has already been mentioned to have an effect on the RAAS but it contributes to the stress response in one other key way. The hypothalamus can communicate directly with muscles and body organs by sending signals through nerves of the autonomic nervous system rather than relying on hormones to send a message. The medulla of adrenal gland is directly innervated by the SNS. In response to SNS stimulation the adrenal medulla can release catecholamines, such as norepinephrine and epinephrine. The catecholamines are partially responsible for the increased vasoconstriction observed in blood vessels, as well as the increased HR, and CO observed in response to stress. The SNS can as mentioned above cause the release of renin from the kidney, which can then cause affect the cardiovascular system via the RAAS. Additionally, the stimulation of the SNS can also release norepinephrine from the central nervous system to affect receptors on the heart (al’ Absi, Wittmers, Erickson, Hatsukami, & Crouse, 2003). So in conclusion psychological stimulation of the SNS affects the body in three ways: it activates the RAAS, the adrenal medulla, and receptors on the heart.

Psychological Stress Induced Renal Reactivity

The major contribution of the kidneys to the stress response is the release of renin in response to SNS arousal. The renin than activates the RAAS, a long biochemical cascade, which cause increases in BP in two ways, it can directly constrict the vasculature and it can cause the retention of water increasing plasma volume in the blood. A study by Clamage, Vander, and Mouw (1977) studied the effects of several psychosocial stimuli on PRA in normotensive, healthy subjects. The study tested 12 (six males, six females) healthy, normotensive, male and female participants, ranging in age from 19-24 years of age. Subjects were screened for and excluded from the study if they had cardiac or kidney diseases and prescriptions for certain medications.