Differential modulation of baroreflex control of heart rate by neuron- vs. glia-derived angiotensin II.
We developed transgenic mice with targeted expression of human renin (hREN) and human angiotensinogen (hAGT) to either neurons (N-AII mice) or glia (G-AII mice) to test the hypothesis that neuronal and glial ANG II may have differential function. Since baseline blood pressure (BP) did not differ between the models (109 +/- 3 vs. 114 +/- 4 mmHg), we stressed the BP regulatory pathway by measuring the heart rate (HR) (baroreflex) response to phenylephrine- and nitroprusside-induced changes in arterial BP. The midpoint of the baroreflex curve (BP50) was reset to a significantly higher BP in N-AII mice (131 +/- 5 mmHg) compared with littermate controls (115 +/- 3 mmHg). Baroreflex gain (slope of BP-HR relation) was similar in N-AII and control mice (12 +/- 1 vs. 14 +/- 2 beats x min(-1) x mmHg(-1)). In contrast, G-AII mice exhibited less of an increase in BP50 (125 +/- 5 mmHg) but a larger decrease in baroreflex gain (8 +/- 1 beats x min(-1) x mmHg(-1)) compared with both control and N-AII mice. Differences in BP50 and gain between N-AII, G-AII, and control mice persisted after parasympathetic blockade with atropine but were eliminated after sympathetic blockade with propranolol, indicating the effects of ANG II were selective for cardiosympathetic arm of the reflex. ANG II-like immunoreactivity was observed more prominently around the paraventricular nucleus and nucleus tractus solitarii in G-AII mice but more prominently in the ventrolateral medulla in N-AII mice. We conclude that ANG II differentially modulates baroreflex control of HR in mice producing ANG II in neurons vs. glia, and its differential function may reflect regional differences in the production of ANG II in cardiovascular control nuclei of the brain.
Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City 52242, USA.
Koji
K
Sakai
Mark W
MW
Chapleau
Satoshi
S
Morimoto
Martin D
MD
Cassell
Curt D
CD
Sigmund
D000804:Angiotensin II / Q000378:metabolism / Q000502:physiology*; D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism; D000809:Angiotensins / Q000096:biosynthesis; D000818:Animals; D017704:Baroreflex; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism; D002320:Cardiovascular Physiological Phenomena; D006339:Heart Rate; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009599:Nitroprusside / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D010656:Phenylephrine / Q000737:chemistry; D011433:Propranolol / Q000737:chemistry; D012083:Renin / Q000235:genetics / Q000378:metabolism
D000809:Angiotensins; D010455:Peptides; D000808:Angiotensinogen; D000804:Angiotensin II; D009599:Nitroprusside; D010656:Phenylephrine; D011433:Propranolol; D012083:Renin