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Resetting of the arterial baroreflex is mediated by central (central command) or peripheral (exercise pressor reflex) mechanisms. The purpose of this study was to determine the effect of somatosensory input from skeletal muscle receptors on resetting of the carotid baroreceptor reflex. Resetting of the baroreflex was determined by measuring carotid sinus threshold pressure (Pth) during a ramp protocol that consisted of a linear increase in sinus pressure from 50 to 250 mmHg at approximately 3 mmHg/s. Experiments were performed in seven alpha-chloralose-anesthetized and vagotomized dogs. To determine the effect of skeletal muscle afferent input on resetting, electrically induced muscle contraction was used to activate mechanically and metabolically senstive afferent fibers, whereas passive stretch of the hindlimb was used to activate predominantly mechanically sensitive afferent fibers. Pth for heart rate (HR) and arterial blood pressure (BP) during the control ramp protocol was 110 +/- 4 and 118 +/- 7 mmHg, respectively. Electrically induced muscle contraction increased hindlimb tension (5.7 +/- 0.4 kg) and significantly increased Pth-HR and Pth-BP above control (135 +/- 6 and 141 +/- 5 mmHg, respectively; P < 0.05). Muscle paralysis prevented the increase in Pth-HR and Pth-BP during ventral root stimulation (104 +/- 7 and 116 +/- 5 mmHg, respectively; P = not significant). Passive muscle stretch (n = 3) increased hindlimb tension (5.9 +/- 0.9 kg) and significantly increased Pth-BP (125 +/- 21 vs. 159 +/- 16 mmHg, control vs. contraction; P < 0.05). There was no difference in the magnitude of Pth resetting between muscle contraction or stretch. The present study demonstrates that activation of skeletal muscle afferent fibers, by either muscle contraction or stretch, increases Pth of the carotid baroreflex. Therefore, neural input from skeletal muscle receptors resets the carotid baroreflex in a manner similar to that ascribed by central command.

A previous study has shown increased Fos-like immunoreactivity (FLI), a marker of neural activation, in the nucleus of the solitary tract (NTS) and the ventrolateral medulla (VLM) after static muscle contraction elicited by electrical stimulation of L7 and S1 ventral roots of the spinal cord in anesthetized, baroreceptor-intact cats. Because the electrically induced static muscle contraction reflexly increased arterial blood pressure, the concomitant activation of the arterial baroreceptor reflex during static muscle contraction may have resulted in some of the FLI labeling that was observed in the medulla. The purpose of this study was to determine regions in the medulla that are activated by muscle contraction in the absence of arterial baroreceptor input. Electrical stimulation of L7 and S1 ventral roots of the spinal cord was used to elicit static muscle contraction, and FLI in the medulla was determined in barointact and barodenervated cats. In barointact contraction cats, FLI was observed in the lateral reticular nucleus (LRN), NTS, lateral tegmental field (FTL), subretrofacial nucleus (SRF), and A1 region of the medulla. In barodenervated contraction cats, FLI increased in the same regions; however, the number of FLI-labeled cells in the NTS, FTL, and A1 region was significantly less than in barointact contraction animals. No significant difference in the number of FLI-labeled cells was found in the LRN and SRF between the two groups. These results clearly demonstrate that cardiovascular regions in the medulla are activated by input from afferent activity originating in skeletal muscle independently of concomitant arterial baroreceptor reflex activation.

The effects of intracerebroventricular administration of physostigmine, a cholinesterase inhibitor, on the cardiovascular responses evoked by static voluntary exercise were investigated using conscious cats. Four cats were trained to press a bar (200-650 g) with one forelimb for at least 20 s. The changes in mean arterial pressure (MAP), heart rate (HR), and developed force during the first five trials in 30 min by each individual cat were averaged, and a mean of the four values was then calculated. After the cats exercised for 30 min, either artificial cerebrospinal fluid (CSF) or physostigmine (5 micrograms) was administered intracerebroventricularly. Before physostigmine, exercise trials by the cats increased MAP and HR by 17 +/- 3 mmHg and 42 +/- 4 beats/min, respectively. Administration of physostigmine did not alter the resting MAP and HR but attenuated the MAP and HR responses to exercise (5-30 min postphysostigmine: MAP = 8 +/- 3 mmHg, HR = 25 +/- 7 beats/min; 30-60 min postphysostigmine: MAP = 4 +/- 3 mmHg, HR = 19 +/- 8 beats/min). Intracerebroventricular administration of CSF had no effect on the cardiovascular responses to static exercise. Pretreatment with the muscarinic antagonist, atropine (25 micrograms icv), blocked the attenuating effects of subsequent intracerebroventricular administration of physostigmine. These results demonstrate that stimulation of central muscarinic receptors attenuates the cardiovascular responses to static exercise by conscious cats. In addition, the present study suggests that there is no tonic effect of central muscarinic receptors on the cardiovascular responses to voluntary exercise.

In this study, we examined Fos-like immunoreactivity (FLI) in the medulla after static muscle contraction induced by stimulation of L7 and S1 ventral roots of the spinal cord in anesthetized cats. The results show that FLI increases in the lateral reticular nucleus, nucleus of the solitary tract, lateral tegmental field, vestibular nucleus, subretrofacial nucleus, and A1 region of the medulla in comparison with these same areas in sham-operated animals (P < 0.05 in each region). In the rostral ventrolateral medulla, FLI distribution in neurons containing phenylethanolamine-N-methyltransferase (PNMT, the synthetic enzyme for epinephrine) was also observed utilizing double-labeling methods. The majority of neurons with PNMT also expressed FLI (66 +/- 4%). These data are in contrast to the results from sham-operated animals showing that 24 +/- 3% of the neurons costained with PNMT (P < 0.05). Our findings indicate that expression of FLI can be used to identify neurons activated during static muscle contraction and support previous studies implicating the ventrolateral medulla as a critical region for expression of the exercise pressor reflex. Furthermore, neurons in the rostral ventrolateral medulla containing PNMT were activated during static muscle contraction.

Reflex response of cardiac sympathetic nerve activity (CSNA) during static contraction of the triceps surae muscle was studied using anesthetized cats. A 1-min contraction was evoked by stimulating the peripheral ends of the cut L7 and S1 ventral roots. CSNA increased 48 +/- 13% immediately after the onset of contraction, which was abolished by cutting the L4-S1 dorsal roots. This rapid increase in CSNA preceded rises in heart rate (13 +/- 1 beats/min) and arterial blood pressure (33 +/- 6 mmHg). When tension development was altered by changing the frequency of ventral root stimulation or the initial muscle length, the CSNA increase depended on the tension developed. Passive stretch of the muscle, which primarily activates mechanoreceptors, increased CSNA by 41 +/- 22%. When the contraction was sustained for 5 min, CSNA remained elevated throughout the contraction despite a fall in tension, suggesting that the later increase in CSNA is caused by factors other than a mechanical event of contraction (e.g., metabolic products). Thus it is suggested that cardiac sympathetic outflow is stimulated due to a reflex arising from the contracting muscle. The increase in CSNA at the initiation of contraction is likely to be caused by a reflex from muscle mechanoreceptors, which is followed by a subsequent increase due to a reflex from muscle metaboreceptors.

Effects of central administration of a cholinesterase inhibitor, physostigmine, on cardiovascular responses to static contraction and passive stretch of the triceps surae were studied using anesthetized cats. Contraction increased mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) by 44 +/- 5 mmHg, 18 +/- 1 beats/min, and 86 +/- 6%, respectively. MAP, HR, and RSNA increased during stretch by 44 +/- 5 mmHg, 15 +/- 1 beats/min, and 61 +/- 4%, respectively. Administration of physostigmine (100 micrograms; 5 microliters) into the third ventricle decreased resting MAP by 22 +/- 3 mmHg and RSNA by 32 +/- 4%, with no effect on HR. Physostigmine attenuated the contraction-evoked responses as MAP, HR, and RSNA increased by 17 +/- 2 mmHg, 3 +/- 1 beats/min, and 31 +/- 6%, respectively. Also, physostigmine blunted MAP, HR, and RSNA responses to stretch (16 +/- 2 mmHg, 4 +/- 1 beats/min, and 9 +/- 6%, respectively). Posterior hypothalamic stimulation increased MAP by 39 +/- 3 mmHg, which was unaffected by physostigmine, despite a lower baseline. Cardiovascular and RSNA responses to contraction and stretch returned to control 90-120 min after physostigmine. Preadministration of the muscarinic antagonist, atropine sulfate (100 micrograms; 5 microliters), blocked the effects of physostigmine. Results suggest central cholinergic stimulation can inhibit the exercise pressor reflex in anesthetized cats.

Group III and IV muscle afferents are active during exercise and relay information from mechano- and metaboreceptors in muscle. We hypothesized that these afferents participate in the regulation of endocrine and metabolic adjustments to exercise. Muscle branches of the femoral nerves were electrically stimulated in 10 anesthetized and paralyzed cats at 3, 20, and 140 times motor threshold, for 10 min at each intensity, recruiting group III afferents at 20 times motor threshold and group III and IV afferents at 140 times motor threshold. Six cats were not stimulated but were otherwise treated as stimulated cats. [3-3H]glucose was infused intravenously, and arterial blood was sampled for analysis of substrates and hormones. Three times motor threshold stimulation induced no changes in measured metabolic parameters. Twenty times motor threshold stimulation elicited increases (P < 0.05 vs. control) in glucose production (8.2 +/- 1.8 mumol.min-1.kg-1) and plasma glucose (0.29 +/- 0.07 mmol/l) and adrenocorticotropic hormone (ACTH; 35 +/- 12 pg/ml). Stimulation at 140 times motor threshold elicited increases (P < 0.05 vs. control) in glucose production (10.2 +/- 5.4 mumol.min-1.kg-1), plasma glucose (0.53 +/- 0.10 mmol/l), ACTH (94 +/- 28 pg/ml), beta-endorphin (17 +/- 6 pg/ml), and Met-enkephalin (15 +/- 2 pg/ml) and decreases (P < 0.05 vs. control) in insulin (0.65 +/- 0.14 microU/ml). Glycerol and glucagon did not change with stimulations. The findings provide evidence for a reflex control from muscle of hormone secretion and mobilization of glucose during exercise.

The effects of hemorrhagic shock on left ventricular dimensions and volume were studied in 15 splenectomized dogs. A 42 +/- 1% decrease in total blood volume caused arterial blood pressure to fall 60% (from 120 +/- 5 to 48 +/- 3 mmHg); the first derivative of left ventricular pressure at a developed pressure of 40 mmHg fell 54% (from 1,930 +/- 94 to 905 +/- 93 mmHg/s, P < 0.05). Cardiac output fell 76% due to a 73% decrease in stroke volume; heart rate was unchanged at the end of hemorrhage but increased 50% during 3 h of sustained shock (from 110 +/- 6 to 166 +/- 8 beats/min, P < 0.05). During hemorrhage the septal-lateral and the anterior-posterior end-diastolic dimensions fell to a greater extent (7.8 mm, -21% and 7.0 mm, -18%, respectively) than the apex-base dimension (2.3 mm, -3.3%, P < 0.05). As a result of these dimensional changes, left ventricular end-diastolic volume fell 39% (from 48 +/- 2 to 28 +/- 1 cm3, P < 0.01). End-systolic dimensions fell in the same proportion during hemorrhage, resulting in a 30% decrease in end-systolic volume (from 30 +/- 2 to 21 +/- 1 cm3, P < 0.05). After 120 min of sustained shock, all end-diastolic dimensions remained unchanged, but end-systolic dimensions and volume increased significantly from values measured at end hemorrhage (P < 0.05), causing ejection fraction and stroke volume to fall to a greater extent. This study confirms a pronounced reduction in the minor axes of the left ventricle during hemorrhagic shock with subsequent reduction in ventricular function.

The aim of this study was to determine if the reflex increase in renal sympathetic nerve activity (RSNA) during static (isometric) muscle contraction evokes renal vasoconstriction and decreases renal blood flow. RSNA, renal blood flow velocity, and arterial pressure were measured simultaneously during isometric contraction of the hindlimb triceps surae muscle in eight chloralose-anesthetized cats. A 1-min contraction was evoked by stimulating the peripheral ends of the cut L7 and S1 ventral roots. RSNA and mean arterial pressure (MAP) increased 41 +/- 14% (SE) and 50 +/- 10 mmHg during static contraction, whereas mean renal blood flow velocity (MRBV) decreased 14 +/- 5%. Calculated renal vascular resistance increased 73 +/- 20% during the contraction. The increase in RSNA preceded the decrease in MRBV by 20 s. Passive mechanical stretch of the muscle increased RSNA 21 +/- 12% but did not alter MRBV. Renal denervation abolished the decrease in MRBV during isometric contraction but only attenuated the rise in MAP. Cutting the L4-S1 dorsal roots or muscle paralysis abolished the MRBV and MAP responses. Thus reflex stimulation of RSNA from the contracting muscle can induce renal vasoconstriction and decrease renal blood flow.

Little is known about the mechanisms responsible for activation of sympathoadrenal function during exercise. We hypothesized that sympathoadrenal discharge is activated at the onset of exercise by a reflex arising in the contracting muscle. Adrenal sympathetic nerve activity (SNA) was recorded during 1 min stimulation of the tibial nerve at two times motor threshold, before and during neuromuscular blockade, in 12 alpha-chloralose-anesthetized rats. Static muscle contractions, induced by stimulation before neuromuscular blockade, were repeated during ganglionic blockade (n = 6) to specifically test reflex activation of preganglionic activity to the adrenal gland. During static contraction, adrenal SNA rapidly increased (P less than 0.05) to a maximum of 89 +/- 12% above basal and then declined, reaching basal levels after 30 s of muscle contraction. Tibial nerve stimulation during neuromuscular blockade had no effect on adrenal SNA. In most rats, adrenal SNA decreased with ganglionic blockade, indicating postganglionic as well as preganglionic innervation of the adrenal gland. During ganglionic blockade, static muscle contractions elicited a 140 +/- 21% increase in adrenal preganglionic SNA. In conclusion, static muscle contraction reflexly increases SNA to the adrenal gland, providing a mechanism for sympathoadrenal activation at the onset of exercise.

To determine the role of reflex neural mechanisms for hormonal, metabolic, heart rate (HR), and blood pressure (MABP) changes during static exercise, seven health young males performed 10-min periods of two-legged static knee extension both during control and during epidural anesthesia. Comparisons were made at identical absolute (29 Nm) and relative [15% maximal voluntary contraction (MVC)] force. Afferent nerve blockade was verified by hypesthesia below T10-T12 and attenuated postexercise ischemic pressor response. Leg strength was reduced to 67 +/- 5% of control. At same relative force, increases in MABP and HR occurred more rapidly without than with epidural anesthesia (P less than 0.05). This difference was diminished during identical absolute force. Changes in plasma concentrations of catecholamines followed the pattern of HR and MABP responses, with differences between epidural and control experiments being most pronounced early in the work period. Plasma beta-endorphin was elevated only after control exercise. No response at 15% MVC was found for growth hormone, adrenocorticotropic hormone, insulin, glucagon, cortisol, glycerol, free fatty acids, or glucose (P greater than 0.05). In conclusion, during static exercise with large muscle groups and moderate relative force, modest changes in plasma hormones and metabolites take place. Furthermore, afferent nervous feedback from contracting muscles is important in regulation of blood pressure, heart rate, and catecholamine responses during static exercise in humans.

Renal sympathetic nerve activity (RSNA), arterial blood pressure (AP), and heart rate (HR) were measured during isometric muscle contraction of a hindlimb in chloralose-anesthetized cats. In 14 cats RSNA, AP, and HR increased during a 1-min contraction by 45%, 39 mmHg, and 11 beats/min, respectively; however, in three cats there was a brief initial decrease in RSNA followed by an increase. In 11 cats isometric contraction was maintained for 5 min by alternate stimulation of the L7 and S1 ventral roots. In the first 1 min of sustained contraction, there was a positive correlation (gamma = 0.58, P less than 0.005) between RSNA and tension development. Thereafter RSNA remained elevated despite a tension decrease, and there was no significant correlation between these changes. The RSNA response to contraction of both hindlimbs was greater than that to contraction of either hindlimb alone. Passive stretch of the hindlimb muscle significantly increased RSNA. Thus the initial increase in RSNA during sustained contraction is likely due to activation of muscle mechanoreceptors, whereas the later increase is probably caused by activation of the muscle metaboreceptors.

In an anesthetized dog, injections of capsaicin, a potent stimulator of small myelinated and unmyelinated fibers that originate as free nerve endings, into a neurally intact donor-perfused hindlimb produced a significant (P less than 0.05) increase in mean aortic pressure (20%), heart rate (12%), cardiac output (28%), and respiratory minute volume (97%). Organ blood flows were measured with 25-micrometers radioactive microspheres. During the injection of capsaicin, there was a decrease in renal blood flow (-25%), but liver, spleen, brain, heart, and skeletal muscle flows remained near control values. After section of the afferent neural connection from the donor perfused hindlimb, the responses to the injection of capsaicin were abolished. These reflex cardiovascular and respiratory responses and changes in organ flow caused by stimulation of capsaicin-sensitive receptors in skeletal muscle are similar to those that occur during induced isometric exercise in the hindlimb.

The distribution of cardiac output was analyzed in six dogs, with the animals at rest and running on a level treadmill for 3 min at 3-4 mph (mild exercise) and 3 min at 6-8 mph (moderate exercise). Organ flows were measured using 25-mug-diam radioactive microspheres. Cardiac output averaged 2.5, 4.6, and 5.7 liters/min, for rest, mild exercise, and moderate exercise, respectively. The greatest change was in diaphragmatic flow which increased by 275% with mild exercise and 500% with moderate exercise. Flow to intercostal muscles increased by 160 and 186%, to the exercising gastrocnemius muscle by 153 and 224%, and to cardiac muscle by 57 and 109% during mild and moderate exercise, respectively. Renal and cerebral flows did not change significantly. Significant decreases in flow occurred in the small and large intestines during moderate exercise. It is concluded that the increase in cardiac output during submaximal exercise was redistributed in a manner which limited flow to the brain, intestines, and kidneys and increased flow flow to the diaphragm, heart, and limb muscles.

The purpose of this study was to measure blood flow to various tissues during static muscular contraction in anesthetized cats and to evaluate if the baroreflex modulates the cardiovascular responses to muscular contraction. Contraction of the hindlimb muscles induced by ventral root stimulation caused increases in arterial pressure (delta 37.8 +/- 5.5 mmHg) and heart rate (delta 13.9 +/- 3.1 beats/min). Increases in blood flow to the heart, working skeletal muscles, and selected areas of the central nervous system occurred during muscular contraction. Blood flow to visceral organs did not change during muscular contraction. Baroreceptor-denervated cats showed a greater rise in arterial pressure (delta 55.5 +/- 5.5 mmHg) during muscular contraction than did the baroreceptor-intact cats. However, blood flow responses were similar in both groups. Thus the baroreceptor reflex modulates the pressor response without changing the alteration in blood flow during induced muscular contraction in anesthetized cats.

Although the reflex cardiovascular and ventilatory responses evoked by stimulation of groups III and IV muscle afferents have been extensively investigated, less is known about the effects of stimulation of these afferents on airway caliber. Therefore, in 11 chloralose-anesthetized dogs, we recorded transverse smooth muscle tension from an innervated segment of the trachea, while we stimulated groups III and IV muscle afferents with capsaicin and bradykinin. Injection of both substances into the arterial supply of the skinned hindlimb evoked dose-dependent decreases in tracheal tension, whereas injection into the femoral vein either increased tension or had no effect on it. Injection of capsaicin and bradykinin into the arterial supply of the gracilis muscle also decreased tracheal tension. In addition, cutting the sciatic, gracilis, and femoral nerves abolished the decreases in tracheal tension caused by injection of capsaicin and bradykinin into the arterial supply of the hindlimb. We conclude that chemical stimulation of groups III and IV muscle afferents causes reflux relaxation of tracheal smooth muscle in dogs.

Our purpose was to determine the effects of controlled ventilation with positive end-expired pressure (PEEP) on ventricular dimensions and to relate changes in shape to changes in stroke volume and left ventricular volumes. Left and right ventricular dimensions were measured using biplane cinefluorography of dogs with radiopaque markers implanted in their hearts, and left ventricular volumes were derived from left ventricular dimensions by assuming that the left ventricle conformed to the shape of a nonprolate ellipsoid. As PEEP increased from 0 to 5, 10, and 15 cmH2O, stroke volume fell 36%, and all three left ventricular end-diastolic dimensions fell, with apex-base falling 5%, anterior-posterior falling 7%, and septal-lateral falling nearly twice as much, 12%. This resulted in a 11.3 cm3 fall in left ventricular end-diastolic volume. The right ventricular end-diastolic dimensions changed in opposite directions with respect to each other as the level and PEEP was raised to 15 cmH2O; one axis fell 3.2 mm, and the midpoint of the right ventricular free wall moved outward by 1.7 mm. Thus the fall in cardiac output (and stroke volume) during PEEP was associated with a fall in left ventricular end-diastolic volume and a change both left and right ventricular configurations. It is not known whether the left ventricular septal-lateral narrowing is the consequence of lateral wall compression by the lungs or encroachment on the left ventricle by the septum.

Static exercise performed by conscious cats elicits increases in heart rate (HR), left ventricular systolic pressure (LVSP), and the maximal rate of left ventricular pressure development [LV(dP/dt)max]. The increased HR is mediated primarily by withdrawal of parasympathetic tone, whereas a beta-adrenergic mechanism is responsible for the LV(dP/dt)max increase. In the present study the cardiovascular responses to static exercise in awake cats was recorded before and after alpha-adrenergic blockade. Pressure transducers were implanted into the left ventricle of cats who had been trained operantly to perform static exercise. Significant increases in LVSP, LV(dP/dt)max and HR occurred in all cats during static exercise before blockade. In contrast, alpha-adrenergic blockade (phentolamine, 2.5 mg/kg iv) abolished the exercise-induced increase in LVSP but did not prevent increases in HR and LV(dP/dt)max. The cats performed fewer exercise bouts per day during alpha-blockade than when unblocked. We conclude that an alpha-adrenergic mechanism mediates the increase in LVSP in response to static exercise in conscious cats.

Isometric exercise induced by ventral root stimulation in the anesthetized cat caused heat rate (HR) to increase from 199 +/- 6 beats/min to 206 +/- 6 (P less than 0.001); mean arterial pressure (MAP) from 99 +/- 5.3 mmHg to 112 +/- 5.8 (P less than 0.001); and left ventricular dp/dt at developed pressure of 25 mmHg from 3,960 +/- 204 mmHg/s to 4,380 +/- 220 (P less than 0.001), while end-diastolic pressure remained unchanged. Respiratory volume (RV) increased from 755 +/- 71 ml/min to 1,160 +/- 123 (P less than 0.001). These changes were abolished by cutting the dorsal roots receiving afferents from the exercising muscle. Beta-adrenergic blockade with propranolol (1 mg/kg) abolished the changes in heart rate and contractile state; however, changes in MAP and RV still occurred. Induced isometric exercise causes a small rise in HR with a more marked increase in MAP, the contractile state of the left ventricle and RV. In this preparation the cardiovascular and respiratory changes reflexly originate from contracting skeletal muscle as proven by section of the corresponding dorsal roots, and the cardiovascular changes are mediated in part by activation of beta-adrenergic receptors in the heart.

Static contraction of hindlimb skeletal muscle is known to increase reflexly arterial pressure and heart rate. Potassium is known to be released by the working muscle and is thought to activate the afferents responsible for the reflex cardiovascular responses to muscular contraction. However, it is not known whether potassium, at interstitial concentrations within the range observed during static contraction, is capable of stimulating these afferents. Thus we injected potassium into the gracilis artery of chloralose-anesthetized dogs while we measured interstitial potassium concentrations in the gracilis muscle with potassium-selective electrodes. In 16 dogs, we found that potassium injections, which increased interstitial potassium concentrations by 4.7 +/- 0.3 mM, increased mean arterial pressure by 18 +/- 3 mmHg and heart rate by 12 +/- 8 beats/min; cutting the obturator nerve abolished these increases. These heart rate and blood pressure responses were of short duration (20 +/- 7 s), even though interstitial potassium remained elevated for a period of several minutes. In 5 of the 16 dogs, static contraction of the gracilis muscle for 60 s increased interstitial potassium concentration by 4.3 +/- 0.3 mM. Our data are consistent with the hypothesis that potassium plays a role in causing the reflex cardiovascular responses to static muscular contraction.

The influence on mechanical properties of changes in resting tension over a range from 0.5 to 4.5 g was investigated in 12 isolated cat papillary muscles. At each resting tension, the muscles contracted isometrically with the exception of an externally applied sinusoidal stretch of 0.5% Lmax (deltaL) and 20 Hz. Stiffness (deltaT/deltaL) was determined from deltaL and the peak amplitudes (deltaT) of the individual cycles from the sinusoidal component of tension. Assuming that the muscle and experimental apparatus behaved as a linear second-order mechanical system, it was possible to divide stiffness into its elastic and viscous components. During rest, total stiffness and its components were linearly related to tension. During contraction, stiffness and its elastic component were linearly related to tension. Furthermore, increasing resting tension increased the intercept and decreased the slope of this linear stiffness-tension relationship. The relationship between viscous stiffness and tension during contraction is more complex in that it is a direct relationship at low resting tensions, but an inverse one at high resting tensions.

Chemical stimulation of afferents from the stomach and gallbladder has been shown reflexly to activate the cardiovascular system. It is not known, however, whether stimulating afferents from the pancreas evoke similar reflex activity. Therefore we recorded the cardiovascular responses in cats anesthetized with methoxyflurane, while we applied capsaicin (200 micrograms/ml) and bradykinin (0.001-1,000 micrograms/ml) to the surface of the pancreas. Topically applying these algesic substances evoked cardiovascular responses that included increases in systemic arterial pressure, heart rate, left ventricular dP/dt at 40-mmHg developed pressure and systemic vascular resistance. Bilateral vagotomy at the level of the diaphragm did not diminish the cardiovascular responses evoked by capsaicin or bradykinin. In contrast, removal of the celiac and superior mesenteric ganglia abolished the cardiovascular responses demonstrated previously when capsaicin or bradykinin was applied to the pancreas. We conclude that afferent endings in the pancreas can be stimulated reflexly to increase cardiovascular function in cats. This reflex activation represents a potential mechanism for eliciting the cardiovascular changes observed during acute pancreatitis, particularly the marked vasoconstriction that may lead to renal failure.

Capsaicin was injected into the portal circulation of 29 dogs after a blood delay pathway was constructed between the liver and right heart, through which capsaicin-contaminated blood could be replaced while systemic hemodynamics were maintained constant. Capsaicin (500 micrograms) rapidly decreased left ventricular systolic pressure (-10%), mean arterial pressure (-12%), heart rate (-4%), renal vascular resistance (-7%), maximal rate of left ventricular pressure rise (dP/dtmax) (-12%), and dP/dt at 25 mmHg developed left ventricular pressure (-15%) in animals with paced hearts. Left ventricular end-diastolic pressure did not change. Vagus nerve interruption at the level of the diaphragm did not alter hemodynamic changes occurring during capsaicin injections, but anterior hepatic nerve interruption eliminated the changes, suggesting that the cardiovascular responses were reflex in origin and that the principal afferent pathway traverses the hepatic nerve. This study demonstrates that activation of afferent fiber receptors within the liver tissue can contribute to neural regulation of the cardiovascular system, but the natural stimulus for these receptors is not known.

Studies were designed to characterize the distribution of cardiac output during induced isometric exercise in anesthetized dogs. The response to isometric exercise involved significant increases in heart rate (+12 +/- 3%(SE)), mean arterial pressure (+13 +/- 2%), cardiac output (+26 +/- 8%), and respiratory minute volume (+75 +/- 26%); total peripheral resistance did not change significantly. Significant changes in blood flow were observed during isometric exercise in kidneys (-18 +/- 6%) and contracting limb muscles (+453 +/- 154%). Flow to liver (hepatic artery), spleen, brain, and myocardium remained near control values. Section of spinal dorsal roots L6-L7 abolished the responses to isometric exercise except for the increase in flow to exercising limb muscles. Alpha-adrenergic receptor blockade abolished the decrease in renal blood flow during isometric exercise; however, the increase in flow to exercising limb muscles was not affected by either alpha- or beta-adrenergic blockade.

Alterations in heart rate (HR), left ventricular systolic pressure (LVP), and maximum rate of left ventricular pressure development (LV dP/dtmax) during a Sidman avoidance task were studied in eight chronically prepared dogs. Four of these animals comprised a nonstressed control group. In the experimental group, in addition to phasic increases in HR, LVP, and LV dP/dtmax during the avoidance period of each day, tonic increases in these measures were also observed over the 13 days of the experiment. Left ventricular systolic pressure was found to be least sensitive to the stress procedure inasmuch as the phasic changes were no longer present after the 10th day and tonic levels were within base-line values by the 13th day. When alterations in cardiac activity were observed in the nonstressed animals, there were decreases in function. It was concluded that controlled behavioral stress produces increased cardiac performance without increased bodily activity. It was also hypothesized that preavoidance increases in heart rate in experimental animals were the result of vagal influences on the heart, whereas avoidance increases in HR, LV dP/dtmax, and LVP were functions of increased beta-sympathetic activity on the heart and adaptive peripheral vascular changes.

Recent studies suggest that, in addition to classical humoral metabolic feedback mechanisms, the mobilization of glucoregulatory hormones and glucose in exercise may be regulated by motor centers in the brain. We, therefore, studied the effect of electrically stimulating the posterior hypothalamic locomotor region (PHLR) for 10 min in decorticated (n = 6) and alpha-chloralose-anesthetized (n = 8) cats. Blood pressure and heart rate were measured, and blood samples were drawn for analysis of hormones and metabolites before, during, and after 10 min of PHLR stimulation. Feedback from contracting muscles was prevented by neuromuscular blockade in decorticated cats and by the anesthesia in anesthetized cats. In decorticated cats, PHLR stimulation elicited increases (2 P less than 0.05) in glucose production (delta 54 +/- 16 mumol.min-1.kg-1), plasma glucose (delta 2.2 +/- 0.7 mmol/l), epinephrine (delta 4.9 +/- 1.8 pmol/l), norepinephrine (delta 2.2 +/- 0.9 pmol/l), glucagon (delta 16 +/- 5 pmol/l), decreases (2 P less than 0.05) in plasma insulin (delta 27 +/- 7 pmol/l), and increases (2 P less than 0.05) in blood pressure (delta 48 +/- 9 mmHg) and heart rate (delta 26 +/- 7 beats/min). In anesthetized cats, PHLR stimulation elicited increases (2 P less than 0.05) in glucose production (delta 12 +/- 4 mumol.min-1.kg-1), plasma glucose (delta 0.4 +/- 0.1 mmol/l), blood pressure (delta 39 +/- 7 mmHg), and heart rate (delta 28 +/- 7 beats/min), whereas changes in catecholamine and insulin concentrations did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of acute severe aortic regurgitation on the left ventricle were investigated in conscious, chronically instrumented dogs. Left ventricular dimensions and volumes were measured from biplane cineradiographs of beads positioned near the endocardium. Data were collected before and after the production of aortic regurgitation by a catheter technique. The aortic regurgitation resulted in increases in mean aortic pulse pressure from 44 to 73 mmHg (P smaller than 0.001), heart rate from 87 to 122 beats/min (P smaller than 0.02), and left ventricular end-diastolic pressure from 11 to 25 mmHg (P smaller than 0.05). Mean end-diastolic volume rose from 61 to 69 cc (P smaller than 0.001), while end-systolic volume remained unchanged at 37 cc. The end-diastolic dilatation following regurgitation was asymmetrical in that the increase in size was due principally to an increase in the septal-lateral axis. The acute volume load of aortic regurgitation was accomplished by an increase in end-diastolic volume, i.e., the Frank-Starling mechanism. The tachycardia probably reflects augmented cardiac sympathetic activity, but the constant end-systolic volume at a similar mean systolic pressure suggests that the net contractile state was unchanged.

We used a constant flow preparation to study the changes in left circumflex coronary arterial (LCCA) pressure and resistance evoked by electrical stimulation of branches of muscle, cutaneous, and mixed nerves in the hindlimb of anesthetized dogs. Stimulation (20 Hz) of all three nerve types at 20, 70, 100, and 200 times the voltage threshold that evoked compound action potentials significantly (P less than 0.05) increased LCCA resistance. Stimulation at three and five times threshold had no effect on this same variable. Cooling the nerve to 2-4 degrees C, temperatures that block myelinated nerve fibers, attenuated but did not abolish the increase in LCCA resistance. Combinations of beta- and alpha-adrenergic and cholinergic blockade established that the biphasic change evoked by nerve stimulation was due to an initial alpha-adrenergic vasoconstriction followed by a metabolite-induced vasodilation. These data demonstrate that stimulation of muscle, cutaneous, or mixed nerve afferent C-fibers increases coronary arterial resistance by alpha-adrenergic vasoconstriction.