Progressive hypertension in dogs by avoidance conditioning and saline infusion.

Abstract

SUMMARY A group of dogs was trained on a free-operant avoidance-conditioning task that evoked acute increases in arterial pressure and heart rate during each of three daily 30-minute sessions. After 15 days of exposure to this procedure under conditions of normal sodium intake, 24-hour mean levels of arterial pressure remained unchanged. Another group of dogs received continuous intrarterial infusion of isotonlc saline at a constant rate of 185 mEq/24 hrs for 15 days, but no avoidance sessions. Again, 24-hour mean levels of arterial pressure did not change significantly. However, 24-hour mean levels of systolic (19.5 ± 6.2 mm Hg) and diastolic (13.7 ± 2.9 mm Hg) pressure rose progressively over a 15-day period in a third group of dogs exposed concurrently to the avoidance schedule and saline infusion procedure. The progressive hypertension was accompanied by no consistent changes in heart rate. These experiments indicate that behavioral stress can potentiate sodium hypertension and provide a new method for the study of physiological and behavioral factors in long-term blood pressure control. (Hypertension 5:286-291, 1983) KEY WORDS • arterial pressure * avoidance conditioning • dogs * heart rate • hypertension • sodium D EVELOPMENT of a model of chronic experimental hypertension in large animals with intact renal functions has remained a formidable experimental challenge. Attempts to produce a "neurogenic" hypertension in primates by exposure to avoidance conditioning over periods of months have been successful on occasion, 1 -2 but other studies 3 -4 have been unable to replicate these results and have concluded that long-term elevations in blood pressure do not result from intermittent evocation of cardiovascular "defense" reflexes alone. Similarly, long-term increases in salt intake can produce sustained hypertension in rodents, 5 but the preponderance of evidence indicates that hypertension is very difficult to produce in larger animals by salt loading procedures. 6Over the past several years, studies in our laboratory have led to the hypothesis that a combination of avoid- ance conditioning and saline infusion could generate a reliable model of chronic experimental hypertension. These studies and others 7 " 1 ' have shown that free-operant avoidance conditioning procedures are associated with characteristic cardiovascular changes in chronically-instrumented dogs during intervals of hours immediately preceding, as well as during avoidance-performance sessions. The pre-avoidance response consists of a progressive rise in arterial pressure mediated solely by increases in total peripheral resistance, while heart rate and cardiac output remain stable or decrease. This response appears to be a peripheral concomitant of attention to the environment, since it occurs only in well-trained dogs who have learned to quietly await the onset of the avoidance session, and then initiate avoidance behavior promptly following the onset of the stimulus. By contrast, the avoidance performance session is associated with a ...

Sympathoadrenal Stress Reactivity Is a Predictor of Future Blood Pressure

“…34,40 One possible mechanism explaining the actual relationship between stress reactivity and development of hypertension could be the direct effect of frequent increases in blood pressure on the vasculature. However, transient blood pressure elevations are not capable of developing sustained blood pressure elevations, per se, in animal models, 11,12 although care should be taken to extrapolate these findings to humans. Our data indicate that activity in the sympathetic nervous system may have implications for later development of hypertension independent of blood pressure.…”

“…Intermittent pressure elevations could lead to structural vascular changes, but attempts to produce irreversible, sustained blood pressure elevations purely as a consequence of transient increases of blood pressure in dogs have not been successful. 11,12 Another possible link between hyperreactivity and development of hypertension is a direct effect of catecholamines. Sympathetic stimulation is known to be a trophic factor for vascular hypertrophy.…”

Neurogenic pressor episodes fail to cause hypertension, but do induce cardiac hypertrophy.

“…Recently, Anderson et al 17 demonstrated that repeated pressor episodes in dogs by themselves are unable to induce hypertension. However, when these dogs were given a rather high sodium intake, repeated pressor episodes did induce prolonged but reversible hypertension.…”

“…Removal of arterial baroreceptors 16 or central destruction of the nuclei of the solitary tractus 29 tend to cause labile blood pressure where periods of hypertension are offset by periods of hypotension, and the average blood pressure is only minimally elevated. Operant conditioning, as described by Anderson et al 17 is the most promising approach to induce short bursts of blood pressure elevation. However, the method requires a high level of experimental sophistication, the blood pressure responses are smaller and the pressor schedules shorter than with hindquarter compression.…”

High Stress Responsivity Predicts Later Blood Pressure Only in Combination With Positive Family History and High Life Stress

“…Three key examples are (1) the modified social environments that enhance confrontations regarding dominance in mice, rats, and monkeys, 19 -25 (2) the model of Received October 9, 1998; first decision December 4, 1998; revision accepted January 26, 1999 daily exposure to shock avoidance conflict in the borderline hypertensive rat (BHR), 26 -30 and (3) the model of combined daily shock avoidance plus saline infusion in the dog. [31][32][33] Each of the models demonstrates that stress exposure can be a critical factor leading directly to hypertension but also that hypertension will only occur in those animals with high susceptibility due to genetic and/or environmental factors. Recent extensions of Henry's work has shown that hypertension with his model develops in only the most susceptible rat strains, and then only in the aggressive dominant or just subdominant males.…”