Electrically induced static exercise elicits a pressor response in the decerebrate rat

The purpose of this investigation was to determine if activation of the exercise pressor reflex in the decerebrate rat induced circulatory responses comparable to those reported in large mammalian species. To activate both mechanically and metabolically sensitive afferent fibres, static hindlimb contractions were induced by stimulating the cut ends of L4 and L5 spinal ventral roots in Sprague-Dawley rats (300–400 g). To selectively stimulate mechanically sensitive receptors, hindlimb muscles were passively stretched. In intact halothane-anaesthetized animals (n = 10), static contraction and passive stretch induced a decrease in mean arterial pressure (ΔMAP =−17 ± 3 and −8 ± 1 mmHg for contraction and stretch, respectively) and heart rate (HR). In contrast, MAP increased 23 ± 2 mmHg during contraction and 19 ± 3 mmHg during stretch in decerebrate rats (n = 10). These pressor responses were accompanied by a significant tachycardia. In decerebrate animals, the reintroduction of halothane attenuated the increase in MAP and HR caused by both contraction and stretch. In both anaesthetized and decerebrate rats, sectioning the spinal dorsal roots innervating the activated skeletal muscle eliminated responses to contraction and stretch. This finding indicated that an intramuscular neural reflex mediated the response to each stimulus. The results demonstrate that a decerebrate preparation in the rat is a reliable model for the study of the exercise pressor reflex. Development of the model would enable the study of this reflex in a variety of pathological conditions and allow investigation of the mechanisms controlling cardiovascular responses to exercise in health and disease. Afferent signals from contracting skeletal muscle are an important source of neural input to the brain stem during exercise (Alam & Smirk, 1937; Coote et al. 1971; McCloskey & Mitchell, 1972; Kaufman & Forster, 1996). These exercise-induced signals are generated by activation of group III (predominantly mechanically sensitive A-δ fibres) and IV (predominantly metabolically sensitive C fibres) skeletal muscle afferents which reflexively increase arterial blood pressure (ABP) and heart rate (McCloskey & Mitchell, 1972; Kaufman et al. 1984). Haemodynamic regulation by this reflex loop, termed the exercise pressor reflex, is primarily mediated by increased efferent sympathetic nerve activity (Mitchell et al. 1983). The rodent is an attractive candidate for the study of the exercise pressor reflex as disease models (e.g. heart failure, hypertension and diabetes) are readily available or easily produced. This is important as previous studies have suggested the exaggerated increases in ABP, sympathetic nerve activity and vascular resistance to exercise in patients with cardiovascular disease are due, in part, to an overactive exercise pressor reflex (Pickering, 1987; Magnusson et al. 1997; Piepoli et al. 1999). Furthermore, more genomic information is currently known about rodents than about larger mammals, presenting the opportunity to study this reflex at the level of cellular and molecular physiology. Unfortunately, induction of static muscle contraction in the rat has been reported to elicit either no change (Vissing et al. 1991), an increase (Freda et al. 1999) or a decrease in arterial blood pressure (Overton & Stremel, 1992; Toney & Mifflin, 1996). The most obvious difference between these investigations was the method of anaesthesia. It is known that anaesthetic agents influence central haemodynamics as well as the cardiovascular responses to stresses such as haemorrhage and exercise (Vatner, 1978; Longnecker et al. 1982). However, experiments comparing the haemodynamic effects of pharmacological anaesthesia and decerebration in rats have shown that the circulatory responses to haemorrhage in the decerebrate animal closely resemble those elicited in the conscious state (Seyde et al. 1985). Therefore, decerebration, which renders the animal insentient and so obviates the need for anaesthesia, may provide a superior model for the study of cardiovascular control in rodents. The purpose of the present investigation was to compare the effects of static muscle contraction and passive stretch on cardiovascular control in anaesthetized and decerebrate rats. Intramuscular afferent fibres were stimulated by (i) involuntary muscle contractions induced by either electrical stimulation of sectioned spinal ventral roots or direct electrical stimulation of the sciatic nerve and (ii) passive muscle stretch. We hypothesized that the use of a decerebrate model would elicit circulatory responses to exercise similar to those previously observed in humans and large animals (McCloskey & Mitchell, 1972; Fisher & Nutter, 1974; Rowell et al. 1981). A preliminary report of these findings has been published (Smith et al. 2000).