Rat aortic vasoreactivity is altered by old age and hindlimb unloading

Delp, Michael D.; Brown, Melanie; Laughlin, M. Harold; Hasser, Eileen M.

doi:10.1152/jappl.1995.78.6.2079

Cited by 87 publications

(114 citation statements)

References 18 publications

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“…The differential effect of hindlimb unloading on myogenic vs. agonist-induced contractions observed in the present study therefore appears to reflect the different sources of Ca 2ϩ for myogenic and agonist-induced contractions. The results of the present study indicate that hindlimb unloading diminishes the NE-and KCl-induced vasoconstrictor responses of mesenteric arteries in a manner similar to that observed in the thoracic and abdominal aorta (14,16,40,41) and carotid and femoral arteries (41). As originally proposed by Delp et al (16), the diminished vasoconstrictor response following HU could result from reductions in intracellular Ca 2ϩ concentration or alterations in the vascular smooth muscle contractile apparatus.…”

Section: Fig 5 Representative Profiles Of the Vasoconstrictor Dynamsupporting

confidence: 86%

“…Because ϳ20% of the increase in peripheral vascular resistance during orthostasis normally occurs as a result of vasoconstriction in splanchnic organs (42), a diminished constrictor response within the splanchnic vasculature could potentially be an underlying mechanism of hindlimb unloading-induced orthostatic hypotension (55). Numerous studies indicate HU reduces constrictor properties of large conduit arteries (14,16,41,43). In mesenteric arteries, the preponderance of evidence suggests HU diminishes contractile responses (5, 22, 38) (see Ref.…”

Section: Fig 5 Representative Profiles Of the Vasoconstrictor Dynammentioning

confidence: 99%

“…HU rats demonstrate many cardiovascular adaptations characteristic of cardiovascular deconditioning in humans, including a reduced exercise capacity (17, 39), orthostatic hypotension (29, 55), and a diminished capacity to elevate PVR (31, 57). This diminished ability to elevate PVR has been shown to be related to reductions in vasoconstrictor responsiveness of a number of conduit arterial segments (14,16,40,41,43,59) and skeletal muscle arterioles (13) from HU rats. However, because ϳ20% of the increase in PVR during orthostasis normally occurs as a result of vasoconstriction in splanchnic organs (42), a diminished constrictor response within the splanchnic vasculature could potentially be an underlying mechanism for orthostatic hypotension.…”

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confidence: 99%

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Simulated microgravity alters rat mesenteric artery vasoconstrictor dynamics through an intracellular Ca²⁺release mechanism

Colleran

Behnke

Wilkerson

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Colleran PN, Behnke BJ, Wilkerson MK, Donato AJ, Delp MD. Simulated microgravity alters rat mesenteric artery vasoconstrictor dynamics through an intracellular Ca 2ϩ release mechanism. Am J Physiol Regul Integr Comp Physiol 294: R1577-R1585, 2008. First published March 19, 2008 doi:10.1152/ajpregu.00084.2008.-Previous work has shown that orthostatic hypotension associated with cardiovascular deconditioning results from inadequate peripheral vasoconstriction. We used the hindlimb-unloaded (HU) rat in this study as a model to induce cardiovascular deconditioning. The purpose of this study was to test the hypothesis that 14 days of HU diminishes vasoconstrictor responsiveness of mesenteric resistance arteries. Mesenteric resistance arteries from control (n ϭ 43) and HU (n ϭ 44) rats were isolated, cannulated, and pressurized to 108 cm H2O for in vitro experimentation. Myogenic (intralumenal pressure ranging from 30 to 180 cm H2O), KCl (2-100 mM), norepinephrine (NE, 10 Ϫ9 -10 Ϫ4 M) and caffeine (1-20 mM) induced vasoconstriction, as well as the temporal dynamics of vasoconstriction to NE, were determined. The active myogenic and passive pressure responses were unaltered by HU when pressures remained within physiological range. However, vasoconstrictor responses to KCl, NE, and caffeine were diminished by HU, as well as the rate of constriction to NE (C, 14.8 Ϯ 3.6 m/s vs. HU 7.6 Ϯ 1.8 m/s). Expression of sarcoplasmic reticulum Ca 2ϩ ATPase 2 and ryanodine 3 receptor mRNA was unaffected by HU, while ryanodine 2 receptor mRNA and protein expression were diminished in mesenteric arteries from HU rats. These data suggest that HU-induced and microgravity-associated orthostatic intolerance may be due, in part, to an attenuated vasoconstrictor responsiveness of mesenteric resistance arteries resulting from a diminished ryanodine 2 receptor Ca 2ϩ release mechanism.hindlimb unloading; vasoconstrictor responsiveness FOLLOWING EXPOSURE TO WEIGHTLESSNESs, many astronauts experience postflight orthostatic hypotension (6, 52) due, in part, to a diminished ability of the cardiovascular system to rapidly elevate peripheral vascular resistance (PVR) (1,2,8,36,52,53). It has been proposed that the diminished ability to elevate PVR following spaceflight may result from altered function of the afferent limb of the baroreceptors, central integration, sympathetic efferents, or end-organ responsiveness to sympathetic stimulation (8). Evidence for end-organ (vascular) hyporesponsiveness has been provided by Whitson et al. (54) and Levine et al. (27), who reported no difference in preflight vs. postflight PVR during orthostasis despite higher postflight levels of plasma catecholamine concentration and muscle sympathetic nerve activity. Similar reductions in vasoconstrictor responsiveness have been reported by investigators using prolonged bedrest (44, 46). Therefore, evidence suggests endorgan responsiveness to vasoconstrictor stimuli is diminished in humans following microgravity and bedrest deconditioning.In addition, orthostatic intol...

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Section: Fig 5 Representative Profiles Of the Vasoconstrictor Dynamsupporting

confidence: 86%

Section: Fig 5 Representative Profiles Of the Vasoconstrictor Dynammentioning

confidence: 99%

mentioning

confidence: 99%

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Simulated microgravity alters rat mesenteric artery vasoconstrictor dynamics through an intracellular Ca²⁺release mechanism

Colleran

Behnke

Wilkerson

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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“…A number of studies in both humans and animals support this interpretation. For example, reduced endothelium-mediated vasodilatory responses have been reported in vivo (65) and in vitro (12,13,25,33,55,65,71) after hindlimb unloading in rats. In addition, reduced dilation has been reported in the vasculatures of the forearm in patients on bed rest (10,11,29,57) and in astronauts after long-term spaceflight (17).…”

Section: Discussionmentioning

confidence: 99%

Hindlimb unloading alters nitric oxide and autonomic control of resting arterial pressure in conscious rats

Mueller

Foley

Hasser

2005

American Journal of Physiology-Regulatory, Integrative and Comp

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After periods of microgravity or bed rest, individuals often exhibit reduced Vo(2 max), hypovolemia, cardiac and vascular effects, and autonomic dysfunction. Recently, alterations in expression of vascular and central nervous system NO synthase (NOS) have been observed in hindlimb-unloaded (HU) rats, a model used to simulate physiological effects of microgravity or bed rest. We examined the effects of 14 days of hindlimb unloading on hemodynamic responses to systemic NOS inhibition in conscious control and HU rats. Because differences in NO and autonomic regulation might occur after hindlimb unloading, we also evaluated potential differences in resting autonomic tone and effects of NOS inhibition after autonomic blockade. Administration of nitro-L-arginine methyl ester (L-NAME; 20 mg/kg iv) increased mean arterial pressure (MAP) to similar levels in control and HU rats. However, the change in MAP in response to L-NAME was less in HU rats, that had an elevated baseline MAP. In separate experiments, atropine (1 mg/kg iv) increased heart rate (HR) in control but not HU rats. Subsequent administration of the ganglionic blocker hexamethonium (30 mg/kg iv) decreased MAP and HR to a greater extent in HU rats. Administration of L-NAME after autonomic blockade increased MAP in both groups to a greater extent compared with intact conditions. However, the pressor response to L-NAME was still reduced in HU rats. These data suggest that hindlimb unloading in rats reduces peripheral NO as well as cardiac parasympathetic tone. Along with elevations in sympathetic tone, these effects likely contribute to alterations in vascular control and changes in autonomic reflex function following spaceflight or bed rest.

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“…In several vascular beds, there is a diminished endotheliumindependent vasodilation to SNP with advancing age (10,23,60) due possibly to reductions in the net intracellular accumulation of cGMP in smooth muscle (61), and/or a reduced scavenging, or increased production, of O 2 Ϫ (18, 84). With advancing age, cGMP is reduced due, in part, to an increased cGMP-phosphodiesterase activity (61,90), which would attenuate cGMP-mediated relaxations.…”

Section: Vascular Dysfunction With Agementioning

confidence: 99%

Effects of aging and exercise training on spinotrapezius muscle microvascular Po₂ dynamics and vasomotor control

McCullough

Davis

Dominguez

et al. 2011

Journal of Applied Physiology

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McCullough DJ, Davis RT III, Dominguez JM II, Stabley JN, Bruells CS, Behnke BJ. Effects of aging and exercise training on spinotrapezius muscle microvascular PO2 dynamics and vasomotor control. J Appl Physiol 110: 695-704, 2011. First published January 6, 2011 doi:10.1152/japplphysiol.01084.2010.-With advancing age, there is a reduction in exercise tolerance, resulting, in part, from a perturbed ability to match O2 delivery to uptake within skeletal muscle. In the spinotrapezius muscle (which is not recruited during incline treadmill running) of aged rats, we tested the hypotheses that exercise training will 1) improve the matching of O2 delivery to O2 uptake, evidenced through improved microvascular PO2 (PmO 2 ), at rest and throughout the contractions transient; and 2) enhance endothelium-dependent vasodilation in first-order arterioles. Young (Y, ϳ6 mo) and aged (O, Ͼ24 mo) Fischer 344 rats were assigned to control sedentary (YSED; n ϭ 16, and OSED; n ϭ 15) or exercisetrained (YET; n ϭ 14, and OET; n ϭ 13) groups. Spinotrapezius blood flow (via radiolabeled microspheres) was measured at rest and during exercise. Phosphorescence quenching was used to quantify PmO 2 in vivo at rest and across the rest-to-twitch contraction (1 Hz, 5 min) transition in the spinotrapezius muscle. In a follow-up study, vasomotor responses to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) stimuli were investigated in vitro. Blood flow to the spinotrapezius did not increase above resting values during exercise in either young or aged groups. Exercise training increased the precontraction baseline PmO 2 (OET 37.5 Ϯ 3.9 vs. OSED 24.7 Ϯ 3.6 Torr, P Ͻ 0.05); the end-contracting Pm O 2 and the time-delay before Pm O 2 fell in the aged group but did not affect these values in the young. Exercise training improved maximal vasodilation in aged rats to acetylcholine (OET 62 Ϯ 16 vs. OSED 27 Ϯ 16%) and to sodium nitroprusside in both young and aged rats. Endurance training of aged rats enhances the Pm O 2 in a nonrecruited skeletal muscle and is associated with improved vascular smooth muscle function. These data support the notion that improvements in vascular function with exercise training are not isolated to the recruited muscle. microvascular oxygen pressures; muscle contraction; isolated microvessel aging WITH ADVANCING AGE, THERE IS a reduction of muscle function and exercise tolerance, resulting, in part, from perturbations in the capacity to transport and utilize oxygen. The diminished exercise tolerance with age is likely consequent to both central (76) and peripheral (53) alterations; however, old age-related structural [e.g., arterial rarefaction (8)] and functional [e.g., diminished vasodilator capacity (10, 62)] arteriolar adaptations directly compromise the fidelity with which oxygen delivery (Q O 2 ) matches oxygen uptake (V O 2 ) within skeletal muscle (11,17,80). In addition, with advancing age, the microvascular PO 2 (Pm O 2 ; determined by the Q O 2 -to-V O 2 ratio) is significantly reduced ...

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Rat aortic vasoreactivity is altered by old age and hindlimb unloading

Cited by 87 publications

References 18 publications

Simulated microgravity alters rat mesenteric artery vasoconstrictor dynamics through an intracellular Ca²⁺release mechanism

Simulated microgravity alters rat mesenteric artery vasoconstrictor dynamics through an intracellular Ca²⁺release mechanism

Hindlimb unloading alters nitric oxide and autonomic control of resting arterial pressure in conscious rats

Effects of aging and exercise training on spinotrapezius muscle microvascular Po₂ dynamics and vasomotor control

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Rat aortic vasoreactivity is altered by old age and hindlimb unloading

Cited by 87 publications

References 18 publications

Simulated microgravity alters rat mesenteric artery vasoconstrictor dynamics through an intracellular Ca2+release mechanism

Simulated microgravity alters rat mesenteric artery vasoconstrictor dynamics through an intracellular Ca2+release mechanism

Hindlimb unloading alters nitric oxide and autonomic control of resting arterial pressure in conscious rats

Effects of aging and exercise training on spinotrapezius muscle microvascular Po2 dynamics and vasomotor control

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Simulated microgravity alters rat mesenteric artery vasoconstrictor dynamics through an intracellular Ca²⁺release mechanism

Simulated microgravity alters rat mesenteric artery vasoconstrictor dynamics through an intracellular Ca²⁺release mechanism

Effects of aging and exercise training on spinotrapezius muscle microvascular Po₂ dynamics and vasomotor control