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Differential effects of angiotensin II on cardiorespiratory reflexes mediated by nucleus tractus solitarii – a microinjection study in the rat
Author(s) -
Paton Julian F. R.,
Kasparov Sergey
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.00213.x
Subject(s) - baroreceptor , reflex bradycardia , angiotensin ii , microinjection , medicine , endocrinology , reflex , solitary nucleus , bradycardia , losartan , chemoreceptor , angiotensin ii receptor type 1 , heart rate , chemistry , anesthesia , receptor , blood pressure
1 The effect of microinjecting angiotensin II (ANGII) into the nucleus of the solitary tract (NTS) on both baroreceptor and peripheral chemoreceptor reflexes was compared. 2 Experiments were performed in a working heart‐brainstem preparation of rat. Baroreceptors were stimulated by raising perfusion pressure and chemoreceptors were activated with aortic injections of sodium cyanide (0·025%, 25–75 μl). Reflex changes in phrenic nerve activity and heart rate were measured after bilateral NTS microinjection (50 nl) of ANGII (0·5–5000 fmol). 3 NTS microinjection of 5 fmol ANGII elicited a transient (28·2 ± 6 s; mean ± s.e.m.) bradycardia (‐18 ± 3 beats min −1 ), and decreased phrenic nerve activity cycle length and amplitude ( P < 0·05 ). At higher doses of ANGII a similar respiratory response was seen but heart rate changes were inconsistent. 4 The baroreceptor reflex bradycardia was depressed significantly by NTS microinjections of ANGII (5–5000 fmol) in a dose‐dependent manner with the reflex gain decreasing from 1·7 ± 0·16 to 0·66 ± 0·1 beats min −1 mmHg −1 ( P < 0·01 ) at 5000 fmol. Although the chemoreceptor reflex bradycardia was depressed at a low dose of ANGII (5 fmol), all higher doses (50–5000 fmol) produced a dose‐dependent potentiation of the reflex bradycardia (maximally +64 ± 8%). The respiratory component was unaffected. The effects of ANGII on both reflexes were blocked by an ANGII type 1 (AT 1 ) receptor antagonist, losartan (20 μM). 5 The potentiating action of ANGII on the chemoreceptor reflex cardiac response was abolished by a neurokinin type 1 (NK 1 ) receptor blocker (CP‐99,994, 5 μM) but this had no effect on the baroreceptor reflex. 6 AT 1 receptors in the NTS can depress the baroreceptor reflex bradycardia which is independent of NK 1 receptors. The ANGII effect on the cardiac component of the chemoreceptor reflex is bi‐directional being inhibited at low concentrations and potentiated at higher concentrations; the latter involves NK 1 receptors and presumably results from release of substance P.