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Propranolol does not increase the contractile response to epinephrine in endothelium-intact aorta from renal hypertensive rat
310
Abstracts / Autonomic Neuroscience: Basic and Clinical 177 (2013) 297–319
Poster 3.16 Reflex responses of arterial pressure to electrical stimulation of the muscle are enhanced in the ovariectomized rats M. Kurosawa, R. Shimoju (Center Med. Sci., Intl. Univ. Health & Welfare, Japan; Physical Ther., Health & Welfare Sci., Intl. Univ. Grad. Sch. Health & Welfare, Japan), K. Uenishi-Sadakiyo, H. Maruyama (Physical Ther., Health & Welfare Sci., Intl. Univ. Grad. Sch. Health & Welfare, Japan) Pressor responses to mental or psychological stress are enhanced in the postmenopausal women and ovariectomized (OVX) animals, an animal model of postmenopause. However, it is not yet known whether pressor responses to physical stress are also enhanced in the postmenopausal state. In the present study we compared the reflex responses of arterial pressure to somatosensory stimulation, a physical stress, in the OVX animals with those in the sham operated (SHAM) animals. Experiments were performed in urethane anesthetized, artificially ventilated rats. Arterial pressure was recorded from the common carotid artery. Electrical stimulation of the muscle was employed as the somatosensory stimulation. The stimulation was delivered to the tibialis posterior muscle for 30 s at various intensities with low (2 Hz) or high (80 Hz) frequency. In the OVX rats both low and high frequency stimulation produced greater pressor responses than in the SHAM rats. On the other hand, basal (prestimulus) values of the arterial pressure in the OVX rats and in the SHAM rats were not different. Furthermore, since it has been shown that baroreflex is impaired in both the postmenopausal women and OVX rats, we investigated whether the impairment of baroreflex is involved in the augmented presser responses of the OVX animals. After sinoaortic denervation, the electrical stimulation of the muscle also elicited greater pressor responses in the OVX rats than in the SHAM rats. These results demonstrate that the impairment of baroreflex is not a major factor in the augmented responses of arterial pressure to electrical stimulation of the muscle in the OVX rats. Further mechanisms are discussed.
doi:10.1016/j.autneu.2013.08.037
Poster 4.11 Cholinergic control of the murine trachealis muscle via non-vesicular acetylcholine release involving NK1 receptor activation C. Nassenstein, S. Wiegand (Institute of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany), K.S. Lips (Laboratory of Experimental Trauma Surgery, Justus-Liebig-University, Giessen, Germany), G. Li, J. Klein (Department of Pharmacology, Goethe University, Frankfurt am Main, Germany), W. Kummer (Institute of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany) In addition to quantal, vesicular release of acetylcholine (ACh), there is also non-quantal release at the motor endplate which is insufficient to evoke postsynaptic responses unless acetylcholinesterase (AChE) is inhibited. We here addressed potential non-quantal release in the mouse trachea by organ bath experiments and (immuno)histochemical methods. Electrical field stimulation (EFS) of nerve terminals elicited tracheal constriction that is largely due to ACh release (atropine-sensitive) and is not significantly affected by AChE or butyrylcholinesterase (BChE) gene-deficiency. Acute inhibition of both esterases by eserine significantly raised tracheal tone
which was fully sensitive to atropine. This effect was reduced, but not abolished, in either AChE or BChE gene-deficient mice, indicating that both esterases are active in the trachealis muscle. Accordingly, classical enzyme histochemistry demonstrated AChE activity in nerve fibres in the muscle and BChE activity in the smooth muscle cells (labelling specificity validated in respective knockout mice). The eserine-induced increase in tracheal tone was unaffected by vesamicol (10− 5 M), an inhibitor of the vesicular acetylcholine transporter, and by corticosteron (10− 5 M), an inhibitor of organic cation transporters. Hemicholinium-3, an inhibitor of the highaffinity choline transporter-1 (CHT1), slightly reduced the eserine effect at 10− 5 M and completely abrogated it at 10− 4 M. Epithelial denudation by brushing largely reduced the response to eserine but not EFS- and muscarine-induced contractions. Interaction of cholinergic and tachykininergic (substance P acting on NK1 receptor) signalling in the mouse trachea has been previously reported (de Swert et al., Pulm Pharmacol Ther. 2007;20(5):588–95). In the present experimental setup, both an NK1 antagonist and sensory denervation (5 d organ culture) largely diminished EFS-induced and abrogated eserine-induced contraction. These data provide evidence for non-vesicular, non-quantal ACh release in the mouse trachea mediated by CHT1 and triggered by substance P acting upon NK1 receptors. Funded by LOEWE NNCS. doi:10.1016/j.autneu.2013.08.038
Poster 5.7 Propranolol does not increase the contractile response to epinephrine in endothelium-intact aorta from renal hypertensive rat Ana C.C. Bocalon (Faculdade de Ciências Farmacêuticas de Ribeirão Preto-USP), Bruno R. Silva (Faculdade de Medicina de Ribeirão PretoUSP, Ribeirão Preto, SP), Lusiane M. Bendhack (Faculdade de Ciências Farmacêuticas de Ribeirão Preto-USP) Renal hypertension (2K-1C) is characterized by the increased sympathetic activity and oxodative stress induced by angiotensin II. Therefore, the epinephrine plasma levels can potentiate the contractile response in 2K-1C rat aorta. This study aimed to evaluate the effect of inhibition of β-adrenoceptor (β-AR) activation on the contractile response induced by epinephrine in intact endothelium (E+) and in denuded aorta (E−) of 2K-1C rats compared to normotensive sham-operated rats (2K). All the procedures were performed in accordance with the standards and policies of Animal Care and Use Committee of the University of São Paulo. Male rats (180–200 g) were anesthetized with tribromoethanol and after a midline laparotomy a silver clip was placed around the left renal artery. Normotensive two-kidney rats (2K) were only submitted to laparotomy. The systolic blood pressure (SBP) was measured by an indirect tail-cuff method 6 weeks after surgery. Rats were considered to be hypertensive when systolic arterial pressure was higher than 160 mm Hg. Rats were killed and the aortic rings were isolated. Concentration–effect curves were constructed for epinephrine in E+ and E− aortas in the absence (Control) or after incubation with 10 μM propranolol (P+) for 20 min. The maximal effect (ME, in grams of tension) and the potency (pD2) were evaluated. Propranolol did not change the contractile response induced by epinephrine in aortas E− from 2K rats (Control, ME: 2.9 ± 0.2 g; pD2: 7.74 ± 0.09; n = 9) and P+ (ME: 3.7 ± 0.3 g; pD2: 7.48 ± 0.19; n = 4) and 2K-1C (Control, ME: 2.1 ± 0.1 g; pD2: 7.92 ± 0.10; n = 7) and P+ (ME: 2.2 ± 0.2 g; pD2: 8.44 ± 0.78; n = 5). In E+ aorta, propranolol increased the ME to epinephrine in 2K rat aortas from 2.6 ± 01 g; n = 11 to 3.1 ± 0.2 g;
Abstracts / Autonomic Neuroscience: Basic and Clinical 177 (2013) 297–319
n = 6) (P b0.01) and it reduced the pD2 values in 2K-1C rat aortas from 7.37 ± 0.16; n = 9 to 6.70 ± 0.22; n = 4) (P b0.05). Our results indicate that the contractile response induced by epinephrine involves the activation of β-AR in the endothelial cells of 2K rat aortas that leads to a lower contractile responses of 2K rat aorta but not in 2K-1C hypertensive rat aorta. Supported by FAPESP and CNPq. doi:10.1016/j.autneu.2013.08.039
Poster 13.6 Purinergic signalling during neuromuscular transmission of the guinea-pig prostate M. Lam (Nagoya City University, Japan), B. Exintaris (Monash Institute of Pharmaceutical Sciences, Australia), H. Hashitani (Nagoya City University, Japan) The prostate exhibits two types of contractions: coordinated, neurogenic contractions that facilitate ejaculation while spontaneous myogenic activity provides small amplitude contractions that can prevent the stagnation of prostatic fluids. The prostate is sympathetically innervated but our studies find that purinergic signalling as well as cholinergic innervation may also play a role in facilitating prostate contractility. Using conventional tension and intracellular microelectrode recording techniques, we have attempted to further explore neuromuscular transmission in the guinea-pig prostate. Transmitter depletion of noradrenergic nerves by guanethidine (1 μM) reduced the Emax of frequency response curves by 64.3% (P b 0.001, n = 5) and increased the IC50 by 6.5 ± 0.3 μM to 8.7 ± 0.1 μM but did not abolish activity indicating that co-transmitters comprise the residual activity. Desensitising the purinergic P2X receptor with α–β-methylene ATP (10 μM) significantly shifted the frequency response curve to the right and increased the IC50 from 5.1 ± 0.09 μM to 22.8 ± 0.37 μM (P b 0.01, n = 4). Furthermore, excitatory junction potentials recorded from the guinea-pig prostate were sensitive to TTX and α–β-methylene ATP which highlights the significant role of ATP as a postsynaptic co-transmitter in nerve-induced contractions. Stimulation of ATP release may be partly regulated by cholinergic prejunctional activity as muscarinic receptor inhibitor, atropine (1 μM) slightly reduced the IC50 from 18.05 ± 0.5 μM to 11.5 ± 0.1 μM of frequency-response curves (P b 0.05, n = 5). Neurogenic contractions of the prostate may be partially reliant on purinergic and cholinergic activity in conjunction to noradrenergic stimulation and may provide an alternative novel target specific to the prostate to relieve an enhanced prostate tone. doi:10.1016/j.autneu.2013.08.040
Poster 14.9 The population distribution of orthostatic blood pressure responses in older community dwelling adults: Is 40 s the new 20/10? C. Finucane (The Irish Longitudinal Study of Ageing (TILDA), Ireland; St. James’s Hospital, Ireland), M.O. Connell (The Irish Longitudinal Study of Ageing (TILDA), Ireland), C.W. Fan (The Irish Longitudinal Study of Ageing (TILDA), Ireland; St. James’s Hospital, Ireland), C. Soraghan (St. James’s Hospital, Ireland), H. Cronin (The Irish Longitudinal Study of Ageing (TILDA), Ireland), R.A. Kenny (The Irish Longitudinal Study of Ageing (TILDA), Ireland; St. James’s Hospital, Ireland)
311
Introduction: Blood pressure responses to standing play an important role in identifying individuals at risk of syncope and unexplained falls. To date no study has examined these responses and prevalence of orthostatic hypotension (OH) at a population level. Methods: Participants (n = 4463) were recruited from The Irish Longitudinal Study on Ageing, a nationally representative cohort study of Irish adults aged 50 and over. Analysis was applied to beat-to-beat blood pressure records from those who underwent an active stand test using continuous non-invasive photoplethysmography (Finometer™). Individuals were identified as having orthostatic hypotension according to ESC guidelines. The spectrum of blood pressure profiles and prevalence of orthostatic hypotension was reported across age, gender and at each time point following standing after reweighting for non-response. Results: Drops in systolic blood pressure increase with age and are higher in females—Males: (50–59) 36.5 mm Hg vs. (80–89) 48.1 mm Hg; Females: (50–59) 42.8 mm Hg vs. (80–89) 49.1 mm Hg. (p b 0.05). Diastolic blood pressure drops remained consistent across age: Males (50–59) 26.1 mm Hg vs. (80–89) 31.6 mm Hg; Females: (50–59) 27.1 mm Hg vs. (80–89) 26.9 mm Hg. The proportion of those with drops of N20 (mm Hg) systolic and/or N10 mm Hg diastolic within 3 min of standing was 97.8% of males and 98.3% of females. The proportion of those with a sustained drop after 40 s of standing increased with age from 6.3% in males and 10.8% in females aged 50–59 to 32% of males and 29% of females in the over 80s. Conclusion: The proportion of those with OH is high according to the 20/10 definition. Timing of the response is important with over a quarter of oldest adults aged N80 demonstrating a sustained blood pressure drop after 40 s. The definition of OH requires refinement to include timing and response morphology to explicitly capture variations in morphology with 40 s being an important cut-off to be considered. doi:10.1016/j.autneu.2013.08.041
Poster 14.12 Bone marrow cells diminish post-ischemic brain injury and accelerate functional recovery in a chronic stage rat model of ischemic stroke Jongman Yoo, Jin-Ju Seo, Jang-Hyeon Eom, Dong-Youn Hwang (Department of Biomedical Science, CHA University, College of Life Science, 502 Yatap-dong, Seongnam, Gyeonggido, Republic of Korea) Even after decades of intensive studies, therapeutic options for patients with stroke are rather limited. Pharmacological approaches as thrombolytic drugs primarily focus on acute stroke recovery, and few options are available for treating chronic stroke patients. In this study, we examined whether systemically administered bone marrow cells (BMCs) could have beneficial effects in a rat model of chronic ischemia. To examine the effects of allogenic BMCs that are delivered during the chronic stage of stroke, we injected the cells at 5 wk, 10 wk, 11 wk and 12 wk post-ischemia both intra-arterially and intravenously and assessed whether BMC delivery promoted behavioral and tissue recovery from ischemia-mediated brain damage. BMC-mediated neurogenesis was prominent in the brains of rats with chronic stroke, and most of the newborn cells eventually became neurons instead of astrocytes. BMC-mediated enhanced neurogenesis coincided with a significant reduction (~50%) in the number of activated microglia, which is consistent with previous reports of enhanced neurogenesis being linked to microglial inactivation. Strikingly, approximately 57% of the BMCs that infiltrated the chronic
Abstracts / Autonomic Neuroscience: Basic and Clinical 177 (2013) 297–319
Poster 3.16 Reflex responses of arterial pressure to electrical stimulation of the muscle are enhanced in the ovariectomized rats M. Kurosawa, R. Shimoju (Center Med. Sci., Intl. Univ. Health & Welfare, Japan; Physical Ther., Health & Welfare Sci., Intl. Univ. Grad. Sch. Health & Welfare, Japan), K. Uenishi-Sadakiyo, H. Maruyama (Physical Ther., Health & Welfare Sci., Intl. Univ. Grad. Sch. Health & Welfare, Japan) Pressor responses to mental or psychological stress are enhanced in the postmenopausal women and ovariectomized (OVX) animals, an animal model of postmenopause. However, it is not yet known whether pressor responses to physical stress are also enhanced in the postmenopausal state. In the present study we compared the reflex responses of arterial pressure to somatosensory stimulation, a physical stress, in the OVX animals with those in the sham operated (SHAM) animals. Experiments were performed in urethane anesthetized, artificially ventilated rats. Arterial pressure was recorded from the common carotid artery. Electrical stimulation of the muscle was employed as the somatosensory stimulation. The stimulation was delivered to the tibialis posterior muscle for 30 s at various intensities with low (2 Hz) or high (80 Hz) frequency. In the OVX rats both low and high frequency stimulation produced greater pressor responses than in the SHAM rats. On the other hand, basal (prestimulus) values of the arterial pressure in the OVX rats and in the SHAM rats were not different. Furthermore, since it has been shown that baroreflex is impaired in both the postmenopausal women and OVX rats, we investigated whether the impairment of baroreflex is involved in the augmented presser responses of the OVX animals. After sinoaortic denervation, the electrical stimulation of the muscle also elicited greater pressor responses in the OVX rats than in the SHAM rats. These results demonstrate that the impairment of baroreflex is not a major factor in the augmented responses of arterial pressure to electrical stimulation of the muscle in the OVX rats. Further mechanisms are discussed.
doi:10.1016/j.autneu.2013.08.037
Poster 4.11 Cholinergic control of the murine trachealis muscle via non-vesicular acetylcholine release involving NK1 receptor activation C. Nassenstein, S. Wiegand (Institute of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany), K.S. Lips (Laboratory of Experimental Trauma Surgery, Justus-Liebig-University, Giessen, Germany), G. Li, J. Klein (Department of Pharmacology, Goethe University, Frankfurt am Main, Germany), W. Kummer (Institute of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany) In addition to quantal, vesicular release of acetylcholine (ACh), there is also non-quantal release at the motor endplate which is insufficient to evoke postsynaptic responses unless acetylcholinesterase (AChE) is inhibited. We here addressed potential non-quantal release in the mouse trachea by organ bath experiments and (immuno)histochemical methods. Electrical field stimulation (EFS) of nerve terminals elicited tracheal constriction that is largely due to ACh release (atropine-sensitive) and is not significantly affected by AChE or butyrylcholinesterase (BChE) gene-deficiency. Acute inhibition of both esterases by eserine significantly raised tracheal tone
which was fully sensitive to atropine. This effect was reduced, but not abolished, in either AChE or BChE gene-deficient mice, indicating that both esterases are active in the trachealis muscle. Accordingly, classical enzyme histochemistry demonstrated AChE activity in nerve fibres in the muscle and BChE activity in the smooth muscle cells (labelling specificity validated in respective knockout mice). The eserine-induced increase in tracheal tone was unaffected by vesamicol (10− 5 M), an inhibitor of the vesicular acetylcholine transporter, and by corticosteron (10− 5 M), an inhibitor of organic cation transporters. Hemicholinium-3, an inhibitor of the highaffinity choline transporter-1 (CHT1), slightly reduced the eserine effect at 10− 5 M and completely abrogated it at 10− 4 M. Epithelial denudation by brushing largely reduced the response to eserine but not EFS- and muscarine-induced contractions. Interaction of cholinergic and tachykininergic (substance P acting on NK1 receptor) signalling in the mouse trachea has been previously reported (de Swert et al., Pulm Pharmacol Ther. 2007;20(5):588–95). In the present experimental setup, both an NK1 antagonist and sensory denervation (5 d organ culture) largely diminished EFS-induced and abrogated eserine-induced contraction. These data provide evidence for non-vesicular, non-quantal ACh release in the mouse trachea mediated by CHT1 and triggered by substance P acting upon NK1 receptors. Funded by LOEWE NNCS. doi:10.1016/j.autneu.2013.08.038
Poster 5.7 Propranolol does not increase the contractile response to epinephrine in endothelium-intact aorta from renal hypertensive rat Ana C.C. Bocalon (Faculdade de Ciências Farmacêuticas de Ribeirão Preto-USP), Bruno R. Silva (Faculdade de Medicina de Ribeirão PretoUSP, Ribeirão Preto, SP), Lusiane M. Bendhack (Faculdade de Ciências Farmacêuticas de Ribeirão Preto-USP) Renal hypertension (2K-1C) is characterized by the increased sympathetic activity and oxodative stress induced by angiotensin II. Therefore, the epinephrine plasma levels can potentiate the contractile response in 2K-1C rat aorta. This study aimed to evaluate the effect of inhibition of β-adrenoceptor (β-AR) activation on the contractile response induced by epinephrine in intact endothelium (E+) and in denuded aorta (E−) of 2K-1C rats compared to normotensive sham-operated rats (2K). All the procedures were performed in accordance with the standards and policies of Animal Care and Use Committee of the University of São Paulo. Male rats (180–200 g) were anesthetized with tribromoethanol and after a midline laparotomy a silver clip was placed around the left renal artery. Normotensive two-kidney rats (2K) were only submitted to laparotomy. The systolic blood pressure (SBP) was measured by an indirect tail-cuff method 6 weeks after surgery. Rats were considered to be hypertensive when systolic arterial pressure was higher than 160 mm Hg. Rats were killed and the aortic rings were isolated. Concentration–effect curves were constructed for epinephrine in E+ and E− aortas in the absence (Control) or after incubation with 10 μM propranolol (P+) for 20 min. The maximal effect (ME, in grams of tension) and the potency (pD2) were evaluated. Propranolol did not change the contractile response induced by epinephrine in aortas E− from 2K rats (Control, ME: 2.9 ± 0.2 g; pD2: 7.74 ± 0.09; n = 9) and P+ (ME: 3.7 ± 0.3 g; pD2: 7.48 ± 0.19; n = 4) and 2K-1C (Control, ME: 2.1 ± 0.1 g; pD2: 7.92 ± 0.10; n = 7) and P+ (ME: 2.2 ± 0.2 g; pD2: 8.44 ± 0.78; n = 5). In E+ aorta, propranolol increased the ME to epinephrine in 2K rat aortas from 2.6 ± 01 g; n = 11 to 3.1 ± 0.2 g;
Abstracts / Autonomic Neuroscience: Basic and Clinical 177 (2013) 297–319
n = 6) (P b0.01) and it reduced the pD2 values in 2K-1C rat aortas from 7.37 ± 0.16; n = 9 to 6.70 ± 0.22; n = 4) (P b0.05). Our results indicate that the contractile response induced by epinephrine involves the activation of β-AR in the endothelial cells of 2K rat aortas that leads to a lower contractile responses of 2K rat aorta but not in 2K-1C hypertensive rat aorta. Supported by FAPESP and CNPq. doi:10.1016/j.autneu.2013.08.039
Poster 13.6 Purinergic signalling during neuromuscular transmission of the guinea-pig prostate M. Lam (Nagoya City University, Japan), B. Exintaris (Monash Institute of Pharmaceutical Sciences, Australia), H. Hashitani (Nagoya City University, Japan) The prostate exhibits two types of contractions: coordinated, neurogenic contractions that facilitate ejaculation while spontaneous myogenic activity provides small amplitude contractions that can prevent the stagnation of prostatic fluids. The prostate is sympathetically innervated but our studies find that purinergic signalling as well as cholinergic innervation may also play a role in facilitating prostate contractility. Using conventional tension and intracellular microelectrode recording techniques, we have attempted to further explore neuromuscular transmission in the guinea-pig prostate. Transmitter depletion of noradrenergic nerves by guanethidine (1 μM) reduced the Emax of frequency response curves by 64.3% (P b 0.001, n = 5) and increased the IC50 by 6.5 ± 0.3 μM to 8.7 ± 0.1 μM but did not abolish activity indicating that co-transmitters comprise the residual activity. Desensitising the purinergic P2X receptor with α–β-methylene ATP (10 μM) significantly shifted the frequency response curve to the right and increased the IC50 from 5.1 ± 0.09 μM to 22.8 ± 0.37 μM (P b 0.01, n = 4). Furthermore, excitatory junction potentials recorded from the guinea-pig prostate were sensitive to TTX and α–β-methylene ATP which highlights the significant role of ATP as a postsynaptic co-transmitter in nerve-induced contractions. Stimulation of ATP release may be partly regulated by cholinergic prejunctional activity as muscarinic receptor inhibitor, atropine (1 μM) slightly reduced the IC50 from 18.05 ± 0.5 μM to 11.5 ± 0.1 μM of frequency-response curves (P b 0.05, n = 5). Neurogenic contractions of the prostate may be partially reliant on purinergic and cholinergic activity in conjunction to noradrenergic stimulation and may provide an alternative novel target specific to the prostate to relieve an enhanced prostate tone. doi:10.1016/j.autneu.2013.08.040
Poster 14.9 The population distribution of orthostatic blood pressure responses in older community dwelling adults: Is 40 s the new 20/10? C. Finucane (The Irish Longitudinal Study of Ageing (TILDA), Ireland; St. James’s Hospital, Ireland), M.O. Connell (The Irish Longitudinal Study of Ageing (TILDA), Ireland), C.W. Fan (The Irish Longitudinal Study of Ageing (TILDA), Ireland; St. James’s Hospital, Ireland), C. Soraghan (St. James’s Hospital, Ireland), H. Cronin (The Irish Longitudinal Study of Ageing (TILDA), Ireland), R.A. Kenny (The Irish Longitudinal Study of Ageing (TILDA), Ireland; St. James’s Hospital, Ireland)
311
Introduction: Blood pressure responses to standing play an important role in identifying individuals at risk of syncope and unexplained falls. To date no study has examined these responses and prevalence of orthostatic hypotension (OH) at a population level. Methods: Participants (n = 4463) were recruited from The Irish Longitudinal Study on Ageing, a nationally representative cohort study of Irish adults aged 50 and over. Analysis was applied to beat-to-beat blood pressure records from those who underwent an active stand test using continuous non-invasive photoplethysmography (Finometer™). Individuals were identified as having orthostatic hypotension according to ESC guidelines. The spectrum of blood pressure profiles and prevalence of orthostatic hypotension was reported across age, gender and at each time point following standing after reweighting for non-response. Results: Drops in systolic blood pressure increase with age and are higher in females—Males: (50–59) 36.5 mm Hg vs. (80–89) 48.1 mm Hg; Females: (50–59) 42.8 mm Hg vs. (80–89) 49.1 mm Hg. (p b 0.05). Diastolic blood pressure drops remained consistent across age: Males (50–59) 26.1 mm Hg vs. (80–89) 31.6 mm Hg; Females: (50–59) 27.1 mm Hg vs. (80–89) 26.9 mm Hg. The proportion of those with drops of N20 (mm Hg) systolic and/or N10 mm Hg diastolic within 3 min of standing was 97.8% of males and 98.3% of females. The proportion of those with a sustained drop after 40 s of standing increased with age from 6.3% in males and 10.8% in females aged 50–59 to 32% of males and 29% of females in the over 80s. Conclusion: The proportion of those with OH is high according to the 20/10 definition. Timing of the response is important with over a quarter of oldest adults aged N80 demonstrating a sustained blood pressure drop after 40 s. The definition of OH requires refinement to include timing and response morphology to explicitly capture variations in morphology with 40 s being an important cut-off to be considered. doi:10.1016/j.autneu.2013.08.041
Poster 14.12 Bone marrow cells diminish post-ischemic brain injury and accelerate functional recovery in a chronic stage rat model of ischemic stroke Jongman Yoo, Jin-Ju Seo, Jang-Hyeon Eom, Dong-Youn Hwang (Department of Biomedical Science, CHA University, College of Life Science, 502 Yatap-dong, Seongnam, Gyeonggido, Republic of Korea) Even after decades of intensive studies, therapeutic options for patients with stroke are rather limited. Pharmacological approaches as thrombolytic drugs primarily focus on acute stroke recovery, and few options are available for treating chronic stroke patients. In this study, we examined whether systemically administered bone marrow cells (BMCs) could have beneficial effects in a rat model of chronic ischemia. To examine the effects of allogenic BMCs that are delivered during the chronic stage of stroke, we injected the cells at 5 wk, 10 wk, 11 wk and 12 wk post-ischemia both intra-arterially and intravenously and assessed whether BMC delivery promoted behavioral and tissue recovery from ischemia-mediated brain damage. BMC-mediated neurogenesis was prominent in the brains of rats with chronic stroke, and most of the newborn cells eventually became neurons instead of astrocytes. BMC-mediated enhanced neurogenesis coincided with a significant reduction (~50%) in the number of activated microglia, which is consistent with previous reports of enhanced neurogenesis being linked to microglial inactivation. Strikingly, approximately 57% of the BMCs that infiltrated the chronic