Inhibition by angiotensin II of baroreceptor‐evoked activity in cardiac vagal efferent nerves in the dog.

Lumbers, Eugenie R.; McCloskey, D.I.; Potter, Erica K.

doi:10.1113/jphysiol.1979.sp012915

Cited by 194 publications

(113 citation statements)

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“…On the other hand, Lumbers et al (1979) reported that the circulating All inhibited the vagal discharge which was evoked by stimulation of arterial baroreceptors. This finding seems to be inconsistent with our results showing an excitatory effects of All on DMV neurones.…”

Section: Discussionmentioning

confidence: 99%

“…AVP facilitates efferent cardiac vagal activity, reflex bradyeardia and reflex inhibition of sympathetic nerve activity, whereas All attenuates all of these (Lumbers, McCloskey & Potter, 1979;Courtice, Kwong, Lumbers & Potter, 1984;Schmid, Guo & Abboud, 1985;Peuler, Edwards, Schmid & Johnson, 1990). Interaction between the effects of the two peptides has also been reported; All attenuates the cardio-inhibitory effects of AVP (Caine, Lumbers & Reid, 1985).…”

Section: Introductionmentioning

confidence: 97%

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Effects of vasopressin and angiotensin II on neurones in the rat dorsal motor nucleus of the vagus, in vitro.

Katafuchi

Muratani

et al. 1992

The Journal of Physiology

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SUMMARY1. Extracellular recordings were made from 297 spontaneously firing neurones in the dorsal motor nucleus of the vagus (DMV) in slice preparations of rat medulla oblongata. Some of the neurones recorded were identified to be vagal motoneurones by antidromic stimulation. The cells fired with a slow irregular pattern at an average rate of 1 1 + 041 spikes/s (mean + S.E.M.).2. Arginine vasopressin (AVP) was applied by perfusion in 196 of the 297 cells. Most of the neurones (190/196, 97 %) were excited by 10-6 M AVP with an increase in firing rate from the basal level of 11 + 0-1 to a maximum of 2-5 + 0-2 spikes/s. There was a dose-dependent relation between the concentration of AVP and the increased firing rate in all DMV neurones tested (n = 38). The threshold concentration of the peptide to produce changes in firing rate was assumed to be about 10-10 M. The remaining six neurones were not affected by application of AVP.3. Application of oxytocin (OXT, 10-6 M) increased the firing rate of all thirtyeight neurones tested. The effects of AVP and OXT on all neurones examined (n = 20 and 4, respectively) still persisted after blocking the synaptic transmission in a low-Ca2+ or Ca2+-free-high-Mg2+ solution, indicating the direct action of both AVP and OXT on the postsynaptic membranes.4. The AVP-induced excitatory responses were completely but reversibly blocked by the Vl-type receptor antagonists, [1-(,f-mercapto-/,,i-cyclopentamethylene-(n = 5) and Phaa-D-Tyr(Et)Phe-Gln-Asn-Lys-Pro-Arg-NH2 (n = 6), whereas a selective and reversible OXT receptor antagonist, desGly-NH2d(CH2)jTyr-(Me)2Thr4]ornithine vasotocin, which suppressed the OXT-induced excitation, did not block the responses to AVP (n = 11). 5. Application of angiotensin II (AII, 10-6 M) to 153 neurones increased the firing rates of 60 (39%) neurones. The firing rate was increased from the basal level of 1-0+041 to a maximum of 1-8+0-2 spikes/s (n = 60). The effect of All was completely abolished by an All receptor antagonist, [Sarl,lle8]angiotensin II (n = 6). There was a dose dependence of the excitatory response on All concentration in all of eleven neurones tested. The threshold concentration was assumed to be about MS 9206 Z -L. MO AND OTHERS 10-9 M. The activity of 5 (3 %) of 153 neurones was decreased, and the remaining 88 (58%) neurones were not affected by AII.6. After blocking synaptic transmission with low-Ca2+-high-Mg2+ medium, ten of sixteen neurones that had been excited by application of All in normal medium still responded to All, and the effects were abolished in the remaining six cells.7.Of fifty-nine cells tested with both AVP and AII applied at 10-6 M, responses of fifty-four (92 %) to AVP were excitation. Of these fifty-four, fifteen were also excited by application of All, one was inhibited, and All had no effect on the remaining thirty-eight (70 %).8. The excitatory responses induced by AVP were completely or partially blocked by simultaneous perfusion of All in normal medium, which were restored by [Sarl,lle8]AII, whereas the appli...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Effects of vasopressin and angiotensin II on neurones in the rat dorsal motor nucleus of the vagus, in vitro.

Katafuchi

Muratani

et al. 1992

The Journal of Physiology

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“…It has been demonstrated in animal studies that the most important mechanism by which angiotensin II affects heart rate is inhibition of the vagus nerve, both at peripheral (Potter, 1982) and central sites (Lumbers et al, 1979;Lee et al, 1980). Captopril, by inhibiting the formation of angiotensin II and decreasing its levels at various neuroeffector sites, may therefore enhance vagal influences on the heart.…”

Section: Methodsmentioning

confidence: 99%

Heart rate control in hypertensive patients treated by captopril.

Sturani¹,

Chiarini²,

Degliesposti³

et al. 1982

Brit J Clinical Pharma

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1 The effect of captopril on autonomic reflex functions has been investigated in fifteen patients with essential hypertension by examining their responses to tests of baroreceptor function (Valsalva's manoeuvre and upright posture), sympathetic nervous system reactivity (cold pressor and mental stress tests) and parasympathetic reactivity (diving test) before and after 3 weeks' treatment with captopril. 2 Captopril significantly reduced arterial blood pressure and resting heart rate but did not affect cardiovascular responses to Valsalva's manoeuvre, upright posture, cold pressor and mental stress tests. 3 The bradycardia associated with the diving reflex test was significantly enhanced by captopril (P less than 0.01). 4 These results indicate that treatment with captopril is associated with increased parasympathetic tone but without inhibition of baroreceptor or sympathetic reflexes.

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“…Therefore, humoral factors in blood can be detected by this area, and it is considered to be ideally suited to the integration of both neural and humoral signals essential for normal autonomic regulation (13,14) . It is possible that the lowering effect of losartan on normal blood pressure is caused by an inhibitory effect of losartan on the glutamate receptor.Since angiotensin II (Ang II) affects the central blood pressure regulatory system, and there is some evidence that Ang II affects blood pressure by modulating baroreflex control of heart rate (HR) (15)(16)(17), it is also possible that AT1 receptor antagonists affect normal blood pressure through modulation of the baroreflex.The aim of this study was to investigate whether a novel AT1 receptor antagonist, TA-606, influences normal blood pressure and its regulatory system as losartan does. We previously demonstrated that TA-606 was a more potent antihypertensive agent than losartan in spontaneously hypertensive rats (18).…”

mentioning

confidence: 99%

“…Since angiotensin II (Ang II) affects the central blood pressure regulatory system, and there is some evidence that Ang II affects blood pressure by modulating baroreflex control of heart rate (HR) (15)(16)(17), it is also possible that AT1 receptor antagonists affect normal blood pressure through modulation of the baroreflex.…”

mentioning

confidence: 99%

Diverse Effects of AT1 Receptor Antagonists on Normal Blood Pressure and Regulatory System.

1999

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An AT1 receptor antagonist, losartan, has been reported to improve survival and quality of life in patients with congestive heart failure as angiotensin converting enzyme inhibitors do. Since many of the patients are normotensive, it may be a drawback if the compound decreases normal blood pressure. In this study, we investigated whether a novel AT1 receptor antagonist, TA-606, which is more potent than losartan, affects normal blood pressure and its regulatory system in comparison with losartan. TA-606 (30 and 100 mg/kg, p.o.) did not change normal blood pressure, whereas losartan (100 mg/kg, p.o.) tended to decrease it. Although EXP3174 (1 and 10 mg/kg, i.v.), an active metabolite of losartan, suppressed the baroreceptor-heart rate (HR) reflex, 606A (1 and 10 mg/kg, i.v.), an active metabolite of TA-606, did not affect it. Since losartan is known to affect the L-glutamate receptor which is part of the central blood pressure regulatory system, we also investigated whether 606A affects L-glutamate receptor binding. We found that 606A did not affect the binding of the L-glutamate receptor, but EXP3174 inhibited the binding with IC50 values of 13.3 tuM. These findings suggest that, even having the same AT1 receptor antagonist properties as losartan and EXP3174, TA-606 and its active metabolite do not influence normal blood pressure or its regulatory system. (Hypertens Res 1999; 22: 121-127) Key Words: TA-606, losartan, AT1 receptor antagonist, baroreceptor-heart rate reflex, blood pressure regulation An AT1 receptor antagonist, losartan, has been reported to improve survival and quality of life of patients with congestive heart failure (1) as angiotensin converting enzyme inhibitors (2, 3) do, which are considered to be good treatments for patients with hypertension. However, hypotensive action of these agents may limit their usage in heart failure patients. Excessively low blood pressure may induce ischemia in multiple organs, and it was reported that blood pressure excessively lowered by antihypertensive agents (< 85 mmHg in diastolic blood pressure) was related to poor prognosis in patients with ischemic heart disease; i. e. , J curve phenomenon (4).Losartan is known as the first nonpeptide AT1 receptor antagonist developed for clinical use (5), and was reported to affect normal blood pressure; by lowering it even at regular clinical doses (6, 7) . In addition to AT1 receptor antagonism, losartan was reported to affect the glutamate receptor which is involved in the central blood pressure regulatory system, including the baroreflex (8, 16). L-glutamate is known as an important neurotransmitter in the medulla oblongata in the central blood pressure regulatory system (9-11). It is also known that this area lacks a blood-brain barrier despite dense vascular supply (12,16). Therefore, humoral factors in blood can be detected by this area, and it is considered to be ideally suited to the integration of both neural and humoral signals essential for normal autonomic regulation (13,14) . It is possible that the low...

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Inhibition by angiotensin II of baroreceptor‐evoked activity in cardiac vagal efferent nerves in the dog.

Cited by 194 publications

References 19 publications

Effects of vasopressin and angiotensin II on neurones in the rat dorsal motor nucleus of the vagus, in vitro.

Effects of vasopressin and angiotensin II on neurones in the rat dorsal motor nucleus of the vagus, in vitro.

Heart rate control in hypertensive patients treated by captopril.

Diverse Effects of AT1 Receptor Antagonists on Normal Blood Pressure and Regulatory System.

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