The Intrinsic Brain Iso-Renin-Angiotensin System in the Rat: Its Possible Role in Central Mechanisms of Blood Pressure Regulation

Ganten, D; Hutchinson, J. S.; Schelling, Pierre

doi:10.1042/cs048265s

Cited by 54 publications

(41 citation statements)

References 7 publications

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“…The threshold concentrations of AVP and All were estimated to be about 10-1lM and 10-9M, respectively. The normal concentrations of AVP and All in the cerebrospinal fluid (CSF) of rats have been reported to be 101 and 3 x 1010 to 10--9 M, respectively (Ganten, Hutchinson & Schelling, 1975; Dogterom, Van Wimersma Greidanus & Swaab, 1977). However, since concentrations of the peptides near the cell bodies might be much higher than those in the CSF when they are released locally to act as neurotransmitters/neuromodulators, the concentration of AVP and All used in the present experiments (1010 to 105 M) is considered to be in the physiological range.…”

Section: Discussionmentioning

confidence: 99%

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%

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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“…Compared with normotensive WistarKyoto (WKY) rats, SHR have elevated renin activity 1 and angiotensinlike immunoreactivity 2 in the brain as well as increased levels of angiotensinlike material in the cerebrospinal fluid (CSF). 3 Spontaneously hypertensive rats also show an enhanced pressor response to centrally administered Ang II and they may have an increased number of Ang II receptors in regions of the brain that are involved in cardiovascular regulation. 4 -6 Moreover, acute or chronic intracerebroventricular administration of either saralasin (a specific Ang II receptor antagonist) or captopril (an angiotensin I converting enzyme inhibitor), at doses that were not effective or much less effective when given intravenously, markedly reduced blood pressure in adult SHR and attenuated the development of hypertension in young SHR.…”

Section: Brain Angiotensin II and Baroreceptor Reflex Function In Spomentioning

confidence: 99%

Brain angiotensin II and baroreceptor reflex function in spontaneously hypertensive rats.

et al. 1989

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We examined whether the increase in baroreceptor reflex function previously reported in lifetime-captopril-treated spontaneously hypertensive rats (SHR) was due to an inhibition of brain angiotensin II mechanisms. Pregnant and lactating SHR were given oral captopril (100 mg/kg/day). After weaning, pups were maintained on captopril (50 mg/kg/day) until the study (19-21 weeks). Control rats received tap water. One week before study captopril-treated and control SHR were given an intracerebroventricular infusion of angiotensin II (7.5 ng/hr, osmotic pump) or vehicle (artificial cerebrospinal fluid). Baroreceptor reflex control of heart rate was assessed by the slope of the relation between the change in mean arterial pressure (mm Hg) versus the change in pulse interval (msec beat"'). Arterial pressure was raised or lowered by intravenous bolus injections of phenylephrine or nitroprusside, respectively. Central infusion of angiotensin II had no significant effect on mean arterial pressure in captopril or control SHR (captopril-angiotensin II 125±4 vs. captopril-vehicle 121±2; control-angiotensin II 169±5 vs. control-vehicle 173±7 mm Hg), but it produced a significant rise in basal heart rate (captopril-angiotensin H 371 ±10 vs. captopril-vehicle 323 ±8, p< 0.0002; controlangiotensin II 338 ±7 vs. control-vehicle 312 ±8 beats/min,p< 0.0183) and in daily water intake (captopril-angiotensin II 20.7±2.2 vs. captopril-vehicle 9.8±0.7, p<0.0426; controlangiotensin n 33.1±3.8 vs. control-vehicle 9.0±0.6 ml/100 g body wt, p<0.0001). Moreover, there was a significant decrease in the slope of the relation between the change in mean arterial pressure and the change in pulse interval for lifetime-captopril-treated SHR but only in response to an increase in mean arterial pressure (captopril-angiotensin II 0.88 ±0.06 vs. captopril-vehicle 2.76±0.49, /XO.OOOI; control-angiotensin II 0.63±0.08 vs. control-vehicle 0.50±0.07 mm Hg" 1 ). In response to a decrease in mean arterial pressure, the slopes were: captopril-angiotensin II 0.55±0.06, captopril-vehicle 0.80±0.11; control-angiotensin II 0.73±0.10, control-vehicle 0.79±0.15 mm Hg" 1 . Our findings suggest that decreased brain angiotensin II activity induced by captopril underlies the increased baroreceptor reflex sensitivity in lifetime-captopril-treated SHR. {Hypertension 1989; 14:274-281) P revious studies have implicated brain angiotensin II (Ang II) in the pathogenesis of hypertension in spontaneously hypertensive rats (SHR). Compared with normotensive WistarKyoto (WKY) rats, SHR have elevated renin activity 1 and angiotensinlike immunoreactivity 2 in the brain as well as increased levels of angiotensinlike material in the cerebrospinal fluid (CSF).3 Spontaneously hypertensive rats also show an enhanced From the

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“…Ganten et aJ. 2 found elevated levels of angiotensin-like material in the cerebrospinal fluid of hypertensive rats. Stamler et al 29 reported that specific binding of 125 I-angiotensin II in the area of forebrain that mediates the pressor response to ICV angiotensin II is higher in SHR than in WKY.…”

Section: Table 5 Changes In Urine Volume Urine Osmolality and Urinmentioning

confidence: 99%

“…It is known that the pressor effects of ICV angiotensin II are greater in SHR than in normotensive WKY, 3 and, as noted above, central administration of both converting enzyme inhibitors and angiotensin II antagonists lowers blood pressure in the adult SHR but is without effect in normotensive WKY. 2 ' 4~i In our own experiments, captopril administered ICV at a rate of 1.25 ixg/hr attenuated the pressor effects of ICV angiotensin I by 50% but did not alter the pressor response to central infusion of angiotensin II. Such observations are consistent with the hypothesis that the brain isorenin-angiotensin system plays an important role in the development and maintenance of hypertension in SHR and with the interpretation that centrally administered captopril can prevent the rise in blood pressure in young SHR by inhibiting the formation of angiotensin II in the brain.…”

Section: Table 5 Changes In Urine Volume Urine Osmolality and Urinmentioning

confidence: 99%

Attenuation of the development of spontaneous hypertension in rats by chronic central administration of captopril.

Okuno¹,

Nagahama²,

Lindheimer³

et al. 1983

Hypertension

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SUMMARY Captopril infused into the lateral ventricle (ICV) of adult spontaneously hypertensive rats (SHR) decreases blood pressure. The current study was designed to explore the effects of brain converting-enzyme inhibition in young animals before the development of established hypertension and to characterize changes induced by captopril in a variety of pressor systems that might be responsible for the development of hypertension in this strain. Captopril (1.25 /u.g/0.5 /xl/hr) was infused into male SHR starting at 7 weeks of age. Four weeks later systolic blood pressure was only 157 ± 3.3 compared to 181 ± 3.9 mm Hg in vehicle-infused controls, and the pressor effect of ICVinjected angiotensin I was attenuated by 50%. When the same dose of captopril was infused intravenously, hypertension progressed as in vehicle-treated rats. Serum angiotensin-converting enzyme activity (SACE) and plasma arginine vasopressin (AVP) concentration were significantly higher (p < 0.001 and 0.05, respectively), in the ICV captopril group than in the ICV vehicle group, while plasma aldosterone concentration and renin activity, fluid intake, urine volume, and urinary sodium excretion were similar in the two groups. Peripheral sympathetic nervous system activity assessed in the resting state was not altered by captopril treatment. In addition, AVP content of the telencephalon, diencephalon, mesencephalon, and pons medulla were not altered by ICV captopril. Renin activity was elevated in the telencephalon of ICV captopril-treated animals but unaltered in the other brain regions examined. These data demonstrate that ICV administration of captopril attenuates the development of hypertension in young SHR by mechanisms apparently independent of altered fluid and sodium balance and the sympathoadrenal system. The effect on blood pressure occurs in the absence of changes in renin activity or AVP content of plasma or those brain regions most often associated with blood pressure control. (Hypertension 5: 653-662, 1983) KEY WORDS • captopril • chronic central infusion • blood pressure • spontaneously hypertensive rats * renin-angiotensin-aldosterone system • catecholamines vasopressin

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The Intrinsic Brain Iso-Renin-Angiotensin System in the Rat: Its Possible Role in Central Mechanisms of Blood Pressure Regulation

Cited by 54 publications

References 7 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.

Brain angiotensin II and baroreceptor reflex function in spontaneously hypertensive rats.

Attenuation of the development of spontaneous hypertension in rats by chronic central administration of captopril.

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