The neural control mechanisms responsible for the cardiovascular response to exercise are not yet completely understood. Experimental evidence sug­ gests two theories about the initiation and maintenance of this response. The first, called "central command," is that neural impulses, arising from the central activity that recruits motor units, excite medullary and spinal neuronal circuits that cause the cardiovascular changes during exercise (26, 67, 72). The second is that muscle contraction stimulates afferent endings within the skeletal muscle which in tum reflexly evoke the cardiovascular changes (15,50, 67).These two theories are not mutually exclusive; substan­ tial evidence suggests that both are applicable (54). The "exercise pressor reflex," broadly defined, comprises all of the car­ diovascular changes reflexly induced from contracting skeletal muscle that are responsible for the increase in arterial blood pressure. Here we describe the cardiovascular changes that occur during induced muscular con­ tractions and examine the skeletal muscle afferents and central pathways responsible for this reflex. Recently an exercise depressor reflex has been reported in rabbits (75), but controversy exists over whether the decrease in arterial blood pressure is due to a reflex (54, 58). The most direct method to study the exercise pressor reflex is to use anesthetized animals in which the cut peripheral ends of the ventral roots

The exercise pressor reflex: its cardiovascular effects, afferent mechanisms, and central pathways.

Skeletal muscle blood flow is closely coupled to metabolic demand, and its regulation is believed to be mainly the result of the interplay of neural vasoconstrictor activity and locally derived vas...

Vasodilatory mechanisms in contracting skeletal muscle

The sections in this article are:


1
Reflex Cardiovascular Responses to Muscular Contraction in Anesthetized and Decerebrate Animals
1.1
Sensory Innervation of Skeletal Muscle

1.2
Reflex Autonomic Responses to Stimulation of Muscle Afferents in Anesthetized Animals

1.3
Discharge Properties of Group III and IV Muscle Afferents

1.4
The Site of the First Synapse—The Dorsal Horn

1.5
Role of Spinal Neurotransmitters and Neuromodulators in the Exercise Pressor Reflex

1.6
Pathways Ascending from the Dorsal Horn

1.7
The Ventrolateral Medulla

1.8
Other Central Neural Structures

1.9
Final Common Pathways

1.10
Interaction Between the Arterial Baroreflex and the Exercise Pressor Reflex in Anesthetized and Decerebrate Animals




2
Evidence for the Exercise Pressor Reflex in Humans and Conscious Animals
2.1
Feedback from Contracting Limb Skeletal Muscle in Humans and Conscious Animals

2.2
The Nature of the Stimulus Evoking the Exercise Pressor Reflex




3
Contribution of Peripheral Afferents to the Exercise Hyperpnea
3.1
Afferents from the Exercising limbs

3.2
The Carotid Chemoreceptor Afferents

3.3
Role in Hyperventilation During Heavy Exercise

3.4
The Pulmonary Afferents

3.5
Cardiac Afferents

3.6
Respiratory Muscle Afferents

3.7
Mediation of the Exercise Hyperpnea by Multiple Mechanisms




4
Summary and Conclusions
4.1
Peripheral Afferent Contribution to Circulatory Responses to Exercise

4.2
Peripheral Afferent Contribution to Ventilatory Responses to Exercise

Reflexes Controlling Circulatory, Ventilatory and Airway Responses to Exercise

Vascular tone of resistance arteries and arterioles determines peripheral vascular resistance, contributing to the regulation of blood pressure and blood flow to, and within the body's tissues and organs. Ion channels in the plasma membrane and endoplasmic reticulum of vascular smooth muscle cells (SMCs) in these blood vessels importantly contribute to the regulation of intracellular Ca2+ concentration, the primary determinant of SMC contractile activity and vascular tone. Ion channels provide the main source of activator Ca2+ that determines vascular tone, and strongly contribute to setting and regulating membrane potential, which, in turn, regulates the open-state-probability of voltage gated Ca2+ channels (VGCCs), the primary source of Ca2+ in resistance artery and arteriolar SMCs. Ion channel function is also modulated by vasoconstrictors and vasodilators, contributing to all aspects of the regulation of vascular tone. This review will focus on the physiology of VGCCs, voltage-gated K+ (KV) channels, large-conductance Ca2+-activated K+ (BKCa) channels, strong-inward-rectifier K+ (KIR) channels, ATP-sensitive K+ (KATP) channels, ryanodine receptors (RyRs), inositol 1,4,5-trisphosphate receptors (IP3Rs), and a variety of transient receptor potential (TRP) channels that contribute to pressure-induced myogenic tone in resistance arteries and arterioles, the modulation of the function of these ion channels by vasoconstrictors and vasodilators, their role in the functional regulation of tissue blood flow and their dysfunction in diseases such as hypertension, obesity, and diabetes. © 2017 American Physiological Society. Compr Physiol 7:485-581, 2017.

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles.

This study aimed at evaluating the influence of submaximal isometric contraction on pressure pain thresholds (PPTs) in 14 fibromyalgia (FM) patients and 14 healthy volunteers, before and after skin hypoesthesia. PPTs were determined with pressure algometry over m. quadriceps femoris before, during and following an isometric contraction. Maximum voluntary contraction (MVC) was assessed using a computerized dynamometer. A contraction of 22% MVC on average was held until exhaustion (max. 5 min) and PPTs were assessed every 30 sec. A local anesthetic cream and a control cream were applied following a double-blind design and PPTs were reassessed. In healthy volunteers PPTs increased during contraction (P < 0.001), then decreased after the end of contraction (P < 0.001) but remained above precontraction values during the 5 min of post-contraction assessments (P < 0.001). In FM patients PPTs decreased in the middle of the contraction period (P < 0.05) and remained below precontraction levels during the rest of the contraction period (P < 0.05) and during the 5 min of post-contraction assessment (immediately post-contraction NS; 2.5 min post-contraction P < 0.01; 5 min post-contraction P < 0.05). The normalized PPTs were significantly lower in patients than in controls during contraction (start P < 0.01; middle P < 0.001; end P < 0.001) and at all times during post-contraction assessments (P < 0.001). Anesthetic cream raised PPTs at rest in controls (P < 0.01) but not in FM patients, and did not influence contraction or post-contraction PPTs in either group. Therefore, the increased pressure pain sensibility in FM patients is more pronounced deep to the skin. The observed decrease of PPTs during isometric contraction in FM patients could be due to sensitization of mechanonociceptors caused by muscle ischemia and/or dysfunction in pain modulation during muscle contraction.

Modulation of pressure pain thresholds during and following isometric contraction in patients with fibromyalgia and in healthy controls

Maximal aerobic power and related variables during submaximal work were determined on the bicycle ergometer and on the treadmill in nine long-distance runners and in nine control subjects.

Cardiorespiratory response to treadmill and bicycle exercise in runners.

Maximal aerobic power and related variables during submaximal work were determined on the bicycle and on the rowing ergometer in 9 oarsmen and in 9 control subjects. During submaximal work, heart rate and pulmonary ventilation were similar with the two exercise procedures in each group, but the oarsmen had lower values than the control subjects. Oxygen uptake at a given workload was higher on the rowing ergometer than on the bicycle ergometer for both the oarsmen and the control subjects. During maximal exercise, the control subjects reached significantly lower values on the rowing ergometer than on the bicycle ergometer for maximal oxygen uptake and maximal oxygen pulse. The oarsmen however attained practically the same values on the two ergometers, with a rank difference correlation coefficient of 0.94. The difference between the results obtained in control subjects and in oarsmen supports the concept of training specificity.

Cardiorespiratory response to bicycle and rowing ergometer exercise in oarsmen

Regional blood flow was measured with the microsphere method in conscious dogs under resting conditions and during moderate exercise on the treadmill.

Regional blood flow in response to exercise in conscious dogs.

Previous experiments in the dog have shown that static contractions of the muscles of one limb elicit a reflex increase of resistance in the vessels of the opposite limb, along with an increase of systemic blood pressure. The aim of the present experiments was to examine whether this reflex can cause a redistribution of cardiac output from the resting areas, in favor of the working parts. In 17 anesthetized and ventilated dogs, static contraction of the muscles of the right thigh was elicited with electrodes inserted into these muscles. The carotid sinuses were kept at constant pressure and the vagi cut. During static contractions systemic blood pressure and cardiac output increased by 17.7±3.1 and 24.2±5.5%, respectively. The blood flow measured with an electromagnetic flowmeter decreased by 21.9±5.3% in the femoral artery of the resting limb and increased by 101±21% in the femoral artery of the “active limb∝. Data obtained in six dogs with injection of radioactive microspheres during stimulations show that blood flow decreased not only in the muscles of the resting limb (34±10%), but also in several other resting areas, such as skin (38±8%), kidney (24±8%), gut (38±6%), and tongue (23±3%). The results show that the reflex under study causes a redistribution of the cardiac output during static muscular contractions.

Cardiac output distribution during induced static muscular contractions in the dog.

Introduction: Skeletal muscle contraction elicits an explosive rise in interstitial potassium (K + ) concentration. K + has been considered as one of the most potent vasoactive metabolites in skeletal muscle arterioles. Studies on isolated blood vessels report large relaxations when extracellular [K + ] is increased up to 10 mM. We studied the effects of smaller and physiologically more relevant increases in [K + ] (adding 1, 2, and 3 mM) and compared them with relaxations induced by the endothelium derived hyperpolarizing factor (EDHF). Methods: Rat gluteal arteries were isolated and mounted in an organ bath for isometric tension recording. After precontraction with norepinephrine, acetylcholine or K + was added in control conditions, after removal of the endothelium or in the presence of ouabain or Ba 2+ . Results: Application of 1, 2, or 3 mM K + induced large vasodilatations (up to 75.4% with 3 mM) (N = 40), which were more sustained at the higher concentrations. Removal of the vascular endothelium had no effect on this relaxation. Inhibition of the K ir channels with Ba 2+ did not alter the K + -induced relaxations, although it significantly inhibited the EDHF-mediated relaxation. Incubation with ouabain significantly decreased the K + -and EDHF-induced relaxation. Simultaneous application of Ba 2+ and ouabain totally abolished both K + - and EDHF-induced responses. Conclusion: Even small increases in extracellular K + concentration elicit large endothelium-independent and ouabain-sensitive relaxations in small skeletal muscle arteries. The fact that both K + - and EDHF-induced vasorelaxations show similar characteristics indicates that K + might be the EDHF in this type of artery.

J. L. Pannier

Papers

Cardiorespiratory response to treadmill and bicycle exercise in runners.

Cardiorespiratory response to bicycle and rowing ergometer exercise in oarsmen

Regional blood flow in response to exercise in conscious dogs.

Cardiac output distribution during induced static muscular contractions in the dog.

Potassium potently relaxes small rat skeletal muscle arteries.