Cardiac sympathetic dysfunction in the prehypertensive spontaneously hypertensive rat

Recent studies in prehypertensive spontaneously hypertensive rats (SHR) have shown larger calcium transients and reduced norepinephrine transporter (NET) activity in cultured stellate neurons compared with Wistar-Kyoto (WKY) controls, although the functional significance of these results is unknown....

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Asıl Yazarlar: Shanks, J, Herring, N, Manou-Stathopoulou, S, Lu, C, Li, D, Paterson, D
Materyal Türü: Journal article
Dil:English
Baskı/Yayın Bilgisi: American Physiological Society 2013
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author Shanks, J
Herring, N
Manou-Stathopoulou, S
Lu, C
Li, D
Paterson, D
author_facet Shanks, J
Herring, N
Manou-Stathopoulou, S
Lu, C
Li, D
Paterson, D
author_sort Shanks, J
collection OXFORD
description Recent studies in prehypertensive spontaneously hypertensive rats (SHR) have shown larger calcium transients and reduced norepinephrine transporter (NET) activity in cultured stellate neurons compared with Wistar-Kyoto (WKY) controls, although the functional significance of these results is unknown. We hypothesized that peripheral sympathetic responsiveness in the SHR at 4 wk of age would be exaggerated compared with the WKY. In vivo arterial pressure (under 2% isoflurane) was similar in SHRs (88 ± 2/50 ± 3 mmHg, n = 18) compared with WKYs (88 ± 3/49 ± 4 mmHg, n = 20). However, a small but significant (P < 0.05) tachycardia was observed in the young SHR despite the heart rate response to vagus stimulation (3 and 5 Hz) in vivo being similar (SHR: n = 12, WKY: n = 10). In isolated atrial preparations there was a significantly greater tachycardia during right stellate stimulation (5 and 7 Hz) in SHRs (n = 19) compared with WKYs (n = 16) but not in response to exogenous NE (0.025–5 μM, SHR: n = 10, WKY: n = 10). There was also a significantly greater release of [3H]NE to field stimulation (5 Hz) of atria in the SHR (SHR: n = 17, WKY: n = 16). Additionally, plasma levels of neuropeptide Y sampled from the right atria in vivo were also higher in the SHR (ELISA, n = 12 for both groups). The difference in [3H]NE release between SHR and WKY could be normalized by the NET inhibitor desipramine (1 μM, SHR: n = 10, WKY: n = 8) but not the α2-receptor antagonist yohimbine (1 μM, SHR: n = 7, WKY: n = 8). Increased cardiac sympathetic neurotransmission driven by larger neuronal calcium transients and reduced NE reuptake translates into enhanced cardiac sympathetic responsiveness at the end organ in prehypertensive SHRs.
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spelling oxford-uuid:671ea6b9-b83d-42a5-92d0-13365ae8c63f2022-03-26T18:36:17ZCardiac sympathetic dysfunction in the prehypertensive spontaneously hypertensive ratJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:671ea6b9-b83d-42a5-92d0-13365ae8c63fEnglishSymplectic Elements at OxfordAmerican Physiological Society2013Shanks, JHerring, NManou-Stathopoulou, SLu, CLi, DPaterson, DRecent studies in prehypertensive spontaneously hypertensive rats (SHR) have shown larger calcium transients and reduced norepinephrine transporter (NET) activity in cultured stellate neurons compared with Wistar-Kyoto (WKY) controls, although the functional significance of these results is unknown. We hypothesized that peripheral sympathetic responsiveness in the SHR at 4 wk of age would be exaggerated compared with the WKY. In vivo arterial pressure (under 2% isoflurane) was similar in SHRs (88 ± 2/50 ± 3 mmHg, n = 18) compared with WKYs (88 ± 3/49 ± 4 mmHg, n = 20). However, a small but significant (P < 0.05) tachycardia was observed in the young SHR despite the heart rate response to vagus stimulation (3 and 5 Hz) in vivo being similar (SHR: n = 12, WKY: n = 10). In isolated atrial preparations there was a significantly greater tachycardia during right stellate stimulation (5 and 7 Hz) in SHRs (n = 19) compared with WKYs (n = 16) but not in response to exogenous NE (0.025–5 μM, SHR: n = 10, WKY: n = 10). There was also a significantly greater release of [3H]NE to field stimulation (5 Hz) of atria in the SHR (SHR: n = 17, WKY: n = 16). Additionally, plasma levels of neuropeptide Y sampled from the right atria in vivo were also higher in the SHR (ELISA, n = 12 for both groups). The difference in [3H]NE release between SHR and WKY could be normalized by the NET inhibitor desipramine (1 μM, SHR: n = 10, WKY: n = 8) but not the α2-receptor antagonist yohimbine (1 μM, SHR: n = 7, WKY: n = 8). Increased cardiac sympathetic neurotransmission driven by larger neuronal calcium transients and reduced NE reuptake translates into enhanced cardiac sympathetic responsiveness at the end organ in prehypertensive SHRs.
spellingShingle Shanks, J
Herring, N
Manou-Stathopoulou, S
Lu, C
Li, D
Paterson, D
Cardiac sympathetic dysfunction in the prehypertensive spontaneously hypertensive rat
title Cardiac sympathetic dysfunction in the prehypertensive spontaneously hypertensive rat
title_full Cardiac sympathetic dysfunction in the prehypertensive spontaneously hypertensive rat
title_fullStr Cardiac sympathetic dysfunction in the prehypertensive spontaneously hypertensive rat
title_full_unstemmed Cardiac sympathetic dysfunction in the prehypertensive spontaneously hypertensive rat
title_short Cardiac sympathetic dysfunction in the prehypertensive spontaneously hypertensive rat
title_sort cardiac sympathetic dysfunction in the prehypertensive spontaneously hypertensive rat
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