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Lawrence I Sinoway

Publications and source records attributed to Lawrence I Sinoway.

At least 19 recordsLinked to original sources
PubMed2006

Vasoconstriction seen in coronary bypass grafts during handgrip in humans.

In animal studies, sympathetically mediated coronary vasoconstriction has been demonstrated during exercise. Human studies examining coronary artery dynamics during exercise are technically difficult to perform. Recently, noninvasive transthoracic Duplex ultrasound studies demonstrated that 1) patients with left internal mammary artery (LIMA) grafts to the left anterior descending artery can be imaged and 2) the LIMA blood flow patterns are similar to those seen in normal coronary arteries. Accordingly, subjects with LIMA to the left anterior descending artery were studied during handgrip protocols as blood flow velocity in the LIMA was determined. Beat-by-beat analysis of changes in diastolic coronary blood flow velocity (CBV) was performed in six male clinically stable volunteers (60 +/- 2 yr) during two handgrip protocols. Arterial blood pressure (BP) and heart rate (HR) were also measured, and an index of coronary vascular resistance (CVR) was calculated as diastolic BP/CBV. Fatiguing handgrip performed at [40% of maximal voluntary contraction (MVC)] followed by circulatory arrest did not evoke an increase in CVR (P = not significant). In protocol 2, short bouts of handgrip (15 s) led to increases in CVR (18 +/- 3% at 50% MVC and 20 +/- 8% at 70% MVC). BP was also increased during handgrip. Our results reveal that in conscious humans, coronary vasoconstriction occurs within 15 s of onset of static handgrip at intensities at or greater than 50% MVC. These responses are likely to be due to sympathetic vasoconstriction of the coronary circulation.

Blood Pressure↗
PubMed2006

Interstitial K+ concentration in active muscle after myocardial infarction.

Previous work demonstrated that Na(+)-K(+) pump activity within skeletal muscle is attenuated in myocardial infarction (MI). This may lead to enhanced interstitial K(+) concentration ([K(+)](o)) in the muscle. We tested the hypothesis that [K(+)](o) rises with muscle contraction and that, in rats with MI, the rate of rise in [K(+)](o) is greater than it is in control animals. Microdialysis probes were inserted in the skeletal muscle of six healthy control and six MI rats. The ends of the probes were then attached to the K(+) electrodes, and [K(+)](o) was continuously measured. Muscle contraction was induced by electrical stimulation of the sciatic nerves for 1 min. Stimulation at 1 and 3 Hz increased muscle [K(+)](o) by 14.2% and 44.7% in controls and by 22.9% and 62.8% in MI rats (P < 0.05 vs. controls), respectively. When ouabain, an inhibitor of Na(+)-K(+) pump, was added to the perfusate, muscle [K(+)](o) rose significantly. This effect of ouabain was significantly attenuated in MI animals. In conclusion, when compared with that in control animals, an increase of [K(+)](o) in exercising muscle is augmented in MI rats, likely due to an attenuation of Na(+)-K(+) pump activity.

Animals↗
PubMed2006

Effects of an oral glucose tolerance test on the myogenic response in healthy individuals.

The myogenic response, the inherent ability of blood vessels to rapidly respond to changes in transmural pressure, is involved in local blood flow autoregulation. Animal studies suggest that both acute hyperglycemia and hyperinsulinemia may impair myogenic vasoconstriction. The purpose of this study was to examine the effects of an oral glucose load on brachial mean blood velocity (MBV) during increases in forearm transmural pressure in humans. Eight healthy men and women (38 +/- 5 yr) underwent an oral glucose tolerance test (OGTT). MBV (in cm/s; Doppler ultrasound) responses to a rise in forearm transmural pressure (arm tank suction, -50 mmHg) were studied before and every 30 min for 120 min during the OGTT. Before the start of the OGTT, MBV was lower than baseline values 30 and 60 s after the application of negative pressure. This suggests that myogenic constriction was present. During the OGTT, blood glucose rose from 88 +/- 2 to 120 +/- 6 mg/dl (P < 0.05) and insulin rose from 14 +/- 1 to 101 +/- 32 microU/ml (P < 0.05). Glucose loading attenuated the reduction in MBV with arm suction (Delta-0.73 +/- 0.14 vs. Delta-1.67 +/- 0.43 cm/s and Delta-1.07 +/- 0.14 vs. Delta-2.38 +/- 0.54 cm/s, respectively, during 30 and 60 s of suction postglucose compared with preglucose values; all P < 0.05). We observed no such time effect for myogenic responses during a sham OGTT. In an additional 5 subjects, glucose loading had no effect on brachial diameters with the application of negative pressure. Oral glucose loading leads to attenuated myogenic vasoconstriction in healthy individuals. The role that this diminished postglucose reactivity plays in mediating postprandial hypotension and/or orthostasis needs to be further explored.

Administration, Oral↗
PubMed2006

Muscle sympathetic nerve activity responses to dynamic passive muscle stretch in humans.

It is suggested that mechanoreceptors in muscle play an important role in the exercise pressor reflex. However, it has not been verified whether isolated stimulation of the mechanoreceptors can induce responses in muscle sympathetic nerve activity (MSNA) in young healthy individuals. We tested the hypothesis that passive stretch of muscle can evoke an increase in MSNA in healthy individuals. In 12 young subjects, leg calf muscles were passively stretched, or actively contracted for 5 s followed by a 15-25 s (random length) relaxation period. Stretch and contraction were each repeated 25 times. MSNA, heart rate and blood pressure were analysed, and averaged according to the onset of the force on a beat-by-beat basis. At the 1st to the 3rd heart beat from the onset of stretch, MSNA (199 +/- 30%, P < 0.05) as well as heart rate (102.5 +/- 0.7%, P < 0.05) increased transiently but significantly from the prior stretch baseline (100%), followed (from 3rd to 7th beat from the onset of stretch) by a transient increase in mean blood pressure (101.9 +/- 0.3%, P < 0.05) from the baseline. Similar response patterns were observed during active muscle contractions. The present data show that MSNA responses to isolated stimulation of mechanoreceptors are measurable. Because of baroreflex engagement, the magnitude of the response is small and transient, and the haemodynamic consequences using this protocol may be limited.

Adult↗
PubMed2006

Sympathetic responses to exercise in myocardial infarction rats: a role of central command.

In congestive heart failure (CHF), exaggerated sympathetic activation is observed during exercise, which elicits excess peripheral vasoconstriction. The mechanisms causing this abnormality are not fully understood. Central command is a central neural process that induces parallel activation of motor and cardiovascular systems. This study was undertaken to determine whether central command serves as a mechanism that contributes to the exaggerated sympathetic response to exercise in CHF. In decerebrated rats, renal and lumbar sympathetic nerve responses (RSNA and LSNA, respectively) to 30 s of fictive locomotion were examined. The fictive locomotion was induced by electrical stimulation of the mesencephalic locomotor region (MLR). The study was performed in control animals (fractional shortening > 40%) and animals with myocardial infarctions (MI; fractional shortening < 30%). With low stimulation of the MLR (current intensity = 20 microA), the sympathetic responses were not significantly different in the control (RSNA: +18 +/- 4%; LSNA: +3 +/- 2%) and MI rats (RSNA: +16 +/- 5%; LSNA: +8 +/- 3%). With intense stimulation of the MLR (50 microA), the responses were significantly greater in MI rats (RSNA: +127 +/- 15%; LSNA: +57 +/- 10%) than in the control rats (RSNA: +62 +/- 5%; LSNA: +21 +/- 6%). In this study, the data demonstrate that RSNA and LSNA responses to intense stimulation of the MLR are exaggerated in MI rats. We suggest that intense activation of central command may play a role in evoking exaggerated sympathetic activation and inducing excessive peripheral vasoconstriction during exercise in CHF.

Animals↗
PubMed2006

Renal vasoconstrictor responses to static exercise during orthostatic stress in humans: effects of the muscle mechano- and the baroreflexes.

Renal circulatory adjustments to stress contribute to blood pressure and volume regulation. Both handgrip (HG) and disengagement of baroreflexes with lower body negative pressure (LBNP) can engage the sympathetic nervous system (SNS). However, the effect of simultaneous HG and LBNP on the renal circulation in humans is not known. Eighteen young healthy volunteers were studied. Beat-to-beat changes in renal blood flow velocity (RBV; Duplex Ultrasound), mean arterial pressure (MAP; Finapres) and heart rate (ECG) were monitored during (a) 15 s HG at 30% maximum voluntary contraction (MVC); (b) LBNP at -10 and -30 mmHg (each level for 5 min); and (c) 15 s HG (at 30% MVC) during LBNP at both levels. Renal vascular resistance index (RVR units) was calculated by dividing MAP by RBV. The increases in RVR during HG alone (12 +/- 6%) were not different from the responses noted during combined HG and LBNP (17 +/- 6% at -10 mmHg and 25 +/- 8% at -30 mmHg). These results suggest occlusion occurs between a neural circuit engaged during 15 s of HG (central command and/or the muscle mechanoreflex) and a circuit activated by LBNP. In additional experiments (n = 6), similar non-algebraic summation of RVR was seen during 15 s involuntary biceps contractions (engages only muscle reflexes) and LBNP. With respect to RVR, neural occlusion occurs between baroreflexes and the muscle mechanoreflex. Muscle mechanoreflex mediated renal vasoconstriction during short bouts of HG is not influenced by baroreflex disengagement.

Adult↗
PubMed2006

Influence of sex and active muscle mass on renal vascular responses during static exercise.

During exercise, reflex renal vasoconstriction helps maintain blood pressure and redistributes blood flow to the contracting muscle. Sex and muscle mass have been shown to influence certain cardiovascular responses to exercise. Whether sex and/or muscle mass influence renal vasoconstrictor responses to exercise is unknown. We studied healthy men (n = 10) and women (n = 10) matched for age and body mass index during handgrip (HG, small muscle mass) and quadriceps contraction (QC, large muscle mass) as beat-to-beat changes in renal blood flow velocity (RBV; duplex ultrasound), mean arterial pressure (MAP; Finapres), and heart rate (ECG) were monitored. Renal vascular resistance (RVR) index was calculated as MAP / RBV. Responses to HG vs. QC were compared in 13 subjects. We found that 1) RVR responses to short (15-s) bouts and fatiguing HG were similar in men and women (change in RVR during 15-s HG at 70% of maximum voluntary contraction = 23 +/- 4 and 31 +/- 4% in men and women, respectively, P = not significant); 2) post-HG circulatory responses were similar in men and women; and 3) HG and QC were similar during short (15-s) bouts (change in RVR during HG at 50% of maximum voluntary contraction = 19 +/- 3 and 18 +/- 5% for arm and leg, respectively, P = not significant). Our findings suggest that muscle reflex-mediated renal vasoconstriction is similar in men and women during static exercise. Moreover, muscle mass does not contribute to the magnitude of the reflex renal vasoconstrictor response seen with muscle contraction.

Adaptation, Physiological↗
PubMed2005

Aging augments interstitial K+ concentrations in active muscle of rats.

Skeletal muscle performance declines with advancing age, and the underlying mechanism is not completely understood. A large body of convincing evidence has demonstrated a crucial role for interstitial K+ concentration ([K+]o) in modulating contractile function of skeletal muscle. The present study tested the hypothesis that during muscle contraction there is a greater accumulation of [K+]o in aged compared with adult skeletal muscle. Twitch muscle contraction was induced by electrical stimulation of the sciatic nerves of 8- and 32-mo-old Fischer 344 x Brown Norway rats. Levels of [K+]o were measured continuously by a microdialysis technique with the probes inserted into the gastrocnemius muscle. Stimulation at 1, 3, and 5 Hz elevated muscle [K+]o by 52, 64, and 88% in adult rats, and by 78, 98, and 104% in aged rats, respectively, and the increase was significantly higher in aged than in adult rats. Recovery for [K+]o, as measured by the time for [K+]o to recover by 20 and 50% from peak response after stimulation, was slower in aged rats. Ouabain (5 mM), a specific inhibitor of the Na+-K+ pump, was added in the perfusate to inhibit the reuptake of K+ into the cells to assess the role of the pump in the overall K+ balance. Ouabain elevated muscle [K+]o at rest, and the effect was significantly attenuated in aged animals. The present data demonstrated an augmented [K+]o in aged skeletal muscle compared with adult skeletal muscle, and the data suggested that an alteration in the function of the Na+-K+ pump may contribute, in part, to the deficiency in K+ balance in skeletal muscle of aged rats.

Aging↗
PubMed2005

Vanilloid type 1 receptor and the acid-sensing ion channel mediate acid phosphate activation of muscle afferent nerves in rats.

Reflex cardiovascular responses to contracting skeletal muscle are mediated by mechanical and metabolic stimulation of thin-fiber muscle afferents. Diprotonated phosphate (H2PO4-) excites those thin-fiber nerves and evokes the muscle pressor reflex. The receptors mediating this response are unknown. Thus we examined the role played by purinergic receptors, vanilloid type 1 receptors (VR1), and acid-sensing ion channels (ASIC) in mediating H2PO4- -evoked pressor responses. Phosphate and blocking agents were injected into the arterial blood supply of the hindlimb muscles of 53 decerebrated rats. H2PO4- (86 mM, pH 6.0) increased mean arterial pressure by 25 +/- 2 mmHg, whereas monoprotonated phosphate (HPO4(2-), pH 7.5) had no effect. Pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (a purinergic receptor antagonist, 2 mM) did not block the response. However, capsazepine (a VR1 antagonist, 1 mg/kg) attenuated the reflex by 60% and amiloride (an ASIC blocker, 6 microg/kg) by 52%. Of note, the H2PO4- -induced pressor response was attenuated by 87% when both capsazepine and amiloride were injected before the H2PO4-. In conclusion, VR1 and ASIC mediate the pressor response due to H2PO4-. The H2PO4- -evoked response was greater when VR1 and ASIC blockers were given simultaneously than when the respective blockers were given separately. Our laboratory's previous study has shown that H+ stimulates ASIC (but not VR1) on thin-fiber afferent nerves in evoking the reflex response. Thus VR1 and ASIC are likely to play a coordinated and interactive role in processing the muscle afferent response to H2PO4-. Furthermore, the physiological mechanisms mediating the response to H+ and H2PO4- are likely to be different.

Acid Sensing Ion Channels↗
PubMed2005

Renal vascular response to static handgrip exercise: sympathetic vs. autoregulatory control.

Static exercise causes activation of the sympathetic nervous system, which results in increased blood pressure (BP) and renal vascular resistance (RVR). The question arises as to whether renal vasoconstriction that occurs during static exercise is due to sympathetic activation and/or related to a pressure-dependent renal autoregulatory mechanism. To address this issue, we monitored renal blood flow velocity (RBV) responses to two different handgrip (HG) exercise paradigms in 7 kidney transplant recipients (RTX) and 11 age-matched healthy control subjects. Transplanted kidneys are functionally denervated. Beat-by-beat analyses of changes in RBV (observed via duplex ultrasound), BP, and heart rate were performed during HG exercise in all subjects. An index of RVR was calculated as BP/RBV. In protocol 1, fatiguing HG exercise (40% of maximum voluntary contraction) led to significant increases in RVR in both groups. However, at the end of exercise, RVR was more than fourfold higher in control subjects than in the RTX group (88 vs. 20% increase over baseline; interaction, P < 0.001). In protocol 2, short bouts of HG exercise (15 s) led to significant increases in RVR at higher workloads (50 and 70% of maximum voluntary contraction) in the control subjects (P < 0.001). RVR did not increase in the RTX group. In conclusion, we observed grossly attenuated renal vasoconstrictor responses to exercise in RTX subjects, in whom transplanted kidneys were considered functionally denervated. Our results suggest that renal vasoconstrictor responses to exercise in conscious humans are mainly dependent on activation of a neural mechanism.

Adult↗
PubMed2005

Interstitial ATP and norepinephrine concentrations in active muscle.

BACKGROUND: Sympathetic nervous system activity increases with exercise in normal subjects. Heightened peripheral sympathetic nervous activity and the resultant increased neurovascular levels of norepinephrine (NE) evoke vasoconstriction and serve to maintain blood pressure and perfusion to vital organs. Previous work demonstrated that the interstitial ATP concentrations ([ATP]i) rise in contracting skeletal muscle, and it is known that sympathetic nerves have purinergic P2X receptors. Thus, in this report we tested the hypothesis that elevated ATP would stimulate these receptors and increase interstitial NE concentrations ([NE]i). METHODS AND RESULTS: Muscle interstitial samples were collected from microdialysis probes inserted in the skeletal muscle of rats, and dialysate concentrations of ATP and NE were determined by the high-performance liquid chromatography method. Stretch (0.5 kg of tension) increased [ATP]i by 68% (P<0.05) and [NE]i by 45% (P<0.05) in active muscle. The rise in NEi was linearly linked to the elevated ATPi (r=0.878, P<0.001). [NE]i was also elevated by 76% (P<0.05) after ATP (3 micromol/L) was injected into the arterial blood supply of the hindlimb muscles. The [NE]i response to muscle stretch was blunted after the P2X receptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) was given. Finally, this response was potentiated by the nucleotidase inhibitor 6-N,N-diethyl-beta-gamma-dibromomethylene-D-adenosine-5'-triphosphate (ARL67156). CONCLUSIONS: ATPi released by skeletal muscle during stretch stimulates P2X receptors on the sympathetic nerves and increases the concentration of NEi in the muscle interstitium.

Adenosine Triphosphate↗
PubMed2005

Effects of supplemental oxygen administration on coronary blood flow in patients undergoing cardiac catheterization.

Patients with heart disease are frequently treated with supplemental oxygen. Although oxygen can exhibit vasoactive properties in many vascular beds, its effects on the coronary circulation have not been fully characterized. To examine whether supplemental oxygen administration affects coronary blood flow (CBF) in a clinical setting, we measured in 18 patients with stable coronary heart disease the effects of breathing 100% oxygen by face mask for 15 min on CBF (via coronary Doppler flow wire), conduit coronary diameter, CBF response to intracoronary infusion of the endothelium-dependent dilator ACh and to the endothelium-independent dilator adenosine, as well as arterial and coronary venous concentrations of the nitric oxide (NO) metabolites nitrotyrosine, NO(2)(-), and NO(3)(-). Relative to breathing room air, breathing of 100% oxygen increased coronary resistance by approximately 40%, decreased CBF by approximately 30%, increased the appearance of nitrotyrosine in coronary venous plasma, and significantly blunted the CBF response to ACh. Oxygen breathing elicited these changes without affecting the diameter of large-conduit coronary arteries, coronary venous concentrations of NO(2)(-) and NO(3)(-), or the coronary vasodilator response to adenosine. Administering supplemental oxygen to patients undergoing cardiac catheterization substantially increases coronary vascular resistance by a mechanism that may involve oxidative quenching of NO within the coronary microcirculation.

Acetylcholine↗
PubMed2005

A perspective on the muscle reflex: implications for congestive heart failure.

In this review we examine the exercise pressor reflex in health and disease. The role of metabolic and mechanical stimulation of thin fiber muscle afferents is discussed. The role ATP and lactic acid play in stimulating and sensitizing these afferents is examined. The role played by purinergic receptors subdivision 2, subtype X, vanilloid receptor subtype 1, and acid-sensing ion channels in mediating the effects of ATP and H+ are discussed. Muscle reflex activation in heart failure is then examined. Data supporting the concept that the metaboreflex is attenuated and that the mechanoreflex is accentuated are presented. The role the muscle mechanoreflex plays in evoking renal vasoconstriction is also described.

Animals↗
PubMed2004

Spinal P2X receptor modulates reflex pressor response to activation of muscle afferents.

Static contraction of skeletal muscle evokes increases in blood pressure and heart rate. Previous studies suggested that the dorsal horn of the spinal cord is the first synaptic site responsible for those cardiovascular responses. In this study, we examined the role of ATP-sensitive P2X receptors in the cardiovascular responses to contraction by microdialyzing the P2X receptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) into the L7 level of the dorsal horn of nine anesthetized cats. Contraction was elicited by electrical stimulation of the L7 and S1 ventral roots. Blockade of P2X receptor attenuated the contraction induced-pressor response [change in mean arterial pressure (delta MAP): 16 +/- 4 mmHg after 10 mM PPADS vs. 42 +/- 8 mmHg in control; P < 0.05]. In addition, the pressor response to muscle stretch was also blunted by PPADS (delta MAP: 27 +/- 5 mmHg after PPADS vs. 49 +/- 8 mmHg in control; P < 0.05). Finally, activation of P2X receptor by microdialyzing 0.5 mM alpha,beta-methylene into the dorsal horn significantly augmented the pressor response to contraction. This effect was antagonized by prior PPADS dialysis. These data demonstrate that blockade of P2X receptors in the dorsal horn attenuates the pressor response to activation of muscle afferents and that stimulation of P2X receptors enhances the reflex response, indicating that P2X receptors play a role in mediating the muscle pressor reflex at the first synaptic site of this reflex.

Adenosine Triphosphate↗
PubMed2004

Muscle mechanoreflex and metaboreflex responses after myocardial infarction in rats.

BACKGROUND: During exercise, the sympathetic nervous system is activated and blood pressure and heart rate increase. In heart failure (HF), the muscle metaboreceptor contribution to sympathetic outflow is attenuated and the mechanoreceptor contribution is accentuated. Previous studies suggest that (1) capsaicin stimulates muscle metabosensitive vanilloid receptor subtype 1 (VR1), inducing a neurally mediated pressor response, and (2) activation of ATP-sensitive P2X receptors enhances the pressor response seen when muscle mechanoreceptors are engaged by muscle stretch. Thus, we hypothesized that the pressor response to VR1 stimulation would be smaller and the sensitizing effects of P2X stimulation greater in rats with HF due to chronic myocardial infarction (MI) than in controls. METHODS AND RESULTS: Eight to 14 weeks after coronary ligation, rats with infarcts >35% had an increased left ventricular end-diastolic pressure and a marked increase in heart weight. Capsaicin injected into the arterial supply of the hindlimb increased blood pressure by 39% (baseline, 93.9+/-9.5 mm Hg) in control animals but only by 8% (baseline, 94.8+/-10.1 mm Hg) in rats with large MIs (P<0.05). P2X receptor stimulation by alpha,beta-methylene ATP enhanced the pressor response to muscle stretch by 42% in control animals and by 72% in rats with large MIs (P<0.05). CONCLUSIONS: Compared with control animals, cardiovascular responses to VR1 stimulation are blunted and P2X-mediated responses are augmented in rats with HF owing to large MIs.

Achilles Tendon↗
PubMed2004

Renal blood flow in heart failure patients during exercise.

During exercise, reflex renal vasoconstriction maintains blood pressure and helps in redistributing blood flow to the contracting muscle. Exercise intolerance in heart failure (HF) is thought to involve diminished perfusion in active muscle. We studied the temporal relationship between static handgrip (HG) and renal blood flow velocity (RBV; duplex ultrasound) in 10 HF and in 9 matched controls during 3 muscle contraction paradigms. Fatiguing HG (protocol 1) at 40% of maximum voluntary contraction led to a greater reduction in RBV in HF compared with controls (group main effect: P <0.05). The reduction in RBV early in HG tended to be more prominent during the early phases of protocol 1. Similar RBV was observed in the two groups during post-HG circulatory arrest (isolating muscle metaboreflex). Short bouts (15 s) of HG at graded intensities (protocol 2; engages muscle mechanoreflex and/or central command) led to greater reductions in RBV in HF than controls (P <0.03). Protocol 3, voluntary and involuntary biceps contraction (eliminates central command), led to similar increases in renal vasoconstriction in HF (n=4). Greater reductions in RBV were found in HF than in controls during the early phases of exercise. This effect was not likely due to a metaboreflex or central command. Thus our data suggest that muscle mechanoreflex activity is enhanced in HF and serves to vigorously vasoconstrict the kidney. We believe this compensatory mechanism helps preserve blood flow to exercising muscle in HF.

Blood Flow Velocity↗
PubMed2004

Muscle pressor reflex: potential role of vanilloid type 1 receptor and acid-sensing ion channel.

Reflex cardiovascular responses to muscle contraction are mediated by mechanical and metabolic stimulation of thin muscle afferent fibers. Metabolic stimulants and receptors involved in responses are uncertain. Capsaicin depolarizes thin sensory afferent nerves that have vanilloid type 1 receptors (VR1). Among potential endogenous ligands of thin fibers, H+ has been suggested as a metabolite mediating the reflex muscle response as well as a potential stimulant of VR1. It has also been suggested that acid-sensing ion channels (ASIC) mediate H+, evoking afferent nerve excitation. We have examined the roles of VR1 and ASIC in mediating cardiovascular reflex responses to acid stimulation of muscle afferents in a rat model. In anesthetized rats, injections of capsaicin into the arterial blood supply of triceps surae muscles evoked a biphasic response (n = 6). An initial fall in mean arterial pressure (from baseline of 95.8 +/- 9.5 to 70.4 +/- 4.5 mmHg, P < 0.05 vs. baseline) was followed by an increase (to 131.6 +/- 11.3 mmHg, P < 0.05 vs. baseline). Anandamide (an endogenous substance that activates VR1) induced the same change in blood pressure as did capsaicin. The pressor (but not depressor) component of the response was blocked by capsazepine (a VR1 antagonist) and section of afferent nerves. In decerebrate rats (n = 8), H+ evoked a pressor response that was not blocked by capsazepine but was attenuated by amiloride (an ASIC blocker). In rats (n = 12) pretreated with resiniferatoxin to destroy muscle afferents containing VR1, capsaicin and H+ responses were blunted. We conclude that H+ stimulates ASIC, evoking the reflex response, and that ASIC are likely to be frequently found on afferents containing VR1. The data also suggest that VR1 and ASIC may play a role in processing of muscle afferent signals, evoking the muscle pressor reflex.

Acid Sensing Ion Channels↗