title: Cardiac sympathetic dysfunction in the prehypertensive spontaneously hypertensive rat.
abstract: 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 [(3)H]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 [(3)H]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.
authors.affiliation: Burdon Sanderson Cardiac Science Centre, Department of Physiology, Anatomy and Genetics, Sherrington Building, University of Oxford, Oxford, United Kingdom.
authors.forename: Julia
authors.initials: J
authors.lastname: Shanks
authors.forename: Sotiria
authors.initials: S
authors.lastname: Manou-Stathopoulou
authors.forename: Chieh-Ju
authors.initials: CJ
authors.lastname: Lu
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: David J
authors.initials: DJ
authors.lastname: Paterson
authors.forename: Neil
authors.initials: N
authors.lastname: Herring
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D062186:Arterial Pressure; D020013:Calcium Signaling; D004195:Disease Models, Animal; D004558:Electric Stimulation; D006321:Heart / Q000294:innervation*; D006339:Heart Rate; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D008297:Male; D009478:Neuropeptide Y / Q000097:blood; D009638:Norepinephrine / Q000378:metabolism; D058246:Prehypertension / Q000097:blood / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013233:Stellate Ganglion / Q000378:metabolism / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors; D014630:Vagus Nerve / Q000378:metabolism / Q000503:physiopathology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D058669:Adrenergic alpha-2 Receptor Antagonists; D009478:Neuropeptide Y; D009638:Norepinephrine
keywords: autonomic neurotransmission; cardiac; hypertension; spontaneously hypertensive rat; sympathetic; vagal
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