Differential Effects of Angiotensin II and Angiotensin-(1-7) at the Nucleus Tractus Solitarii of Transgenic Rats with Low Brain Angiotensinogen

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 700-700
Author(s):  
Aurea S Couto ◽  
Ovidiu Baltatu ◽  
Robson A S Santos ◽  
Detlev Ganten ◽  
Michael Bader ◽  
...  
Keyword(s):  
Heart Rate ◽  
Baroreflex Sensitivity ◽  
Renin Angiotensin System ◽  
Nucleus Tractus Solitarii ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Transgenic Rats ◽  
Baroreflex Control ◽  
Sd Rats ◽  
The Brain

P42 The potential importance of permanent alteration of the brain renin-angiotensin system on angiotensin (Ang) II and Ang-(1-7) effects at the level of the nucleus tractus solitarii (NTS) was investigated in transgenic rats with a deficit in brain angiotensinogen production TGR(ASrAOGEN) (TGR). Ang II (10 pmol), Ang-(1-7) (10 pmol) or NaCl (0.9%/ 50 nl) were microinjected into the NTS of urethane-anesthetized TGR (n=28) and Sprague-Dawley (SD, n=22) rats. Mean arterial pressure (MAP) and heart rate (HR) were measured via a femoral artery catheter and the baroreflex control of heart rate was evaluated after increases in MAP induced by phenylephrine (baroreflex bradycardia). Ang II microinjections into the NTS of the TGR induced a higher decrease in MAP and HR (-37 ± 5 mmHg and -69 ± 12.5 beats/min, respectively) in comparison with SD rats (-18 ± 1 mmHg and -51 ± 11 beats/min, respectively). In contrast, changes after Ang-(1-7) microinjections into the NTS of TGR (-6 ± 1 mmHg and -13 ± 5 beats/min) were significantly smaller than that induced in SD (-11 ± 2 mmHg and -24 ± 8 beats/min.). The baroreflex sensitivity was accentuated in TGR in comparison to SD rats (0.69 ± 0.06 vs. 0.44 ± 0.03 ms/ mmHg). Ang II microinjection into the NTS produced similar attenuation in the baroreflex bradycardia in both SD (0.28 ± 0.07 vs. 0.5 ± 0.07 ms/ mmHg, before injection) and TGR (0.44 ± 0.1 vs. 0.82 ± 0.1ms/ mmHg, before injection). Ang-(1-7) microinjection elicited a facilitation of the baroreflex bradycardia in SD (0.62 ± 0.1 vs. 0.4 ± 0.03 ms/ mmHg, before injection). However in TGR, baroreflex bradycardia after Ang-(1-7) was not different from saline microinjection. These results indicate that a permanent inhibition of angiotensinogen synthesis in the brain can lead to a functional up-regulation of Ang II receptors. However, the putative Ang-(1-7) receptors seem to be desensitized in the NTS of these transgenic rats. The alterated baroreflex sensitivity, both before and after Ang microinjection, indicates the functionally relevant decrease in brain Ang in TGR and supports differential regulatory mechanisms for the effects of the two Ang peptides.

Alterations in Blood Pressure and Heart Rate Variabililty in Transgenic Rats with Low Brain Angiotensinogen

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 727-727
Author(s):  
Ovidiu Baltatu ◽  
Ben J Janssen ◽  
Ralph Plehm ◽  
Detlev Ganten ◽  
Michael Bader
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Baroreflex Sensitivity ◽  
Circadian Variation ◽  
Ang Ii ◽  
Transgenic Rats ◽  
Short Term ◽  
Baroreflex Control ◽  
Sd Rats ◽  
The Brain

P191 The brain renin-angiotensin system (RAS) system may play a functional role in the long-term and short-term control of blood pressure (BPV) and heart rate variability (HRV). To study this we recorded in transgenic rats TGR(ASrAOGEN) with low brain angiotensinogen levels the 24-h variation of BP and HR during basal and hypertensive conditions, induced by a low-dose s.c. infusion of angiotensin II (Ang II, 100 ng/kg/min) for 7 days. Cardiovascular parameters were monitored by telemetry. Short-term BPV and HRV were evaluated by spectral analysis and as a measure of baroreflex sensitivity the transfer gain between the pressure and heart rate variations was calculated. During the Ang II infusion, in SD but not TGR(ASrAOGEN) rats, the 24-h rhythm of BP was inverted (5.8 ± 2 vs. -0.4 ± 1.8 mm Hg/group of day-night differences of BP, p< 0.05, respectively). In contrast, in both the SD and TGR(ASrAOGEN) rats, the 24-h HR rhythms remained unaltered and paralleled those of locomotor activity. The increase of systolic BP was significantly reduced in TGR(ASrAOGEN) in comparison to SD rats as previously described, while the HR was not altered in TGR(ASrAOGEN) nor in SD rats. The spectral index of baroreflex sensitivity (FFT gain between 0.3-0.6 Hz) was significantly higher in TGR(ASrAOGEN) than SD rats during control (0.71 ± 0.1 vs. 0.35 ± 0.06, p<0.05), but not during Ang II infusion (0.6 ± 0.07 vs. 0.4 ± 0.1, p>0.05). These results demonstrate that the brain RAS plays an important role in mediating the effects of Ang II on the circadian variation of BP. Furthermore these data are consistent with the view that the brain RAS modulates baroreflex control of HR in rats, with AII having an inhibitory role.

Enhanced isoproterenol-induced cardiac hypertrophy in transgenic rats with low brain angiotensinogen

2006 ◽  
Vol 291 (5) ◽  
pp. H2371-H2376 ◽  
Author(s):  
Luciana A. Campos ◽  
Radu Iliescu ◽  
Marco Antonio Peliky Fontes ◽  
Wolfgang-Peter Schlegel ◽  
Michael Bader ◽  
...  
Keyword(s):  
Heart Rate ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Transgenic Rats ◽  
Baroreflex Control ◽  
Isolated Hearts ◽  
Sd Rats ◽  
The Brain

We have previously shown that a permanent deficiency in the brain renin-angiotensin system (RAS) may increase the sensitivity of the baroreflex control of heart rate. In this study we aimed at studying the involvement of the brain RAS in the cardiac reactivity to the β-adrenoceptor (β-AR) agonist isoproterenol (Iso). Transgenic rats with low brain angiotensinogen (TGR) were used. In isolated hearts, Iso induced a significantly greater increase in left ventricular (LV) pressure and maximal contraction (+dP/d tmax) in the TGR than in the Sprague-Dawley (SD) rats. LV hypertrophy induced by Iso treatment was significantly higher in TGR than in SD rats (in g LV wt/100 g body wt, 0.28 ± 0.004 vs. 0.24 ± 0.004, respectively). The greater LV hypertrophy in TGR rats was associated with more pronounced downregulation of β-AR and upregulation of LV β-AR kinase-1 mRNA levels compared with those in SD rats. The decrease in the heart rate (HR) induced by the β-AR antagonist metoprolol in conscious rats was significantly attenuated in TGR compared with SD rats (−9.9 ± 1.7% vs. −18.1 ± 1.5%), whereas the effect of parasympathetic blockade by atropine on HR was similar in both strains. These results indicate that TGR are more sensitive to β-AR agonist-induced cardiac inotropic response and hypertrophy, possibly due to chronically low sympathetic outflow directed to the heart.

Blockade of AT1 receptors enhances baroreflex control of heart rate in conscious rabbits with heart failure

1996 ◽  
Vol 271 (1) ◽  
pp. R303-R309 ◽  
Author(s):  
H. Murakami ◽  
J. L. Liu ◽  
I. H. Zucker
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Baroreflex Sensitivity ◽  
Vena Cava ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Baroreflex Control ◽  
At1 Antagonist ◽  
Before And After ◽  
Baroreceptor Activation

Because the renin-angiotensin system is activated in heart failure, we hypothesized that angiotensin II (ANG II) plays a role in altering baroreflex sensitivity in the setting of heart failure. Accordingly, we evaluated the baroreflex control of heart rate (HR) in conscious, chronically instrumented rabbits in the normal state and after the establishment of heart failure. Heart failure was induced by rapid ventricular pacing at a rate of 360-380 beats/min for an average of 14.5 +/- 1.4 days. The data were compared with normal rabbits instrumented in a similar fashion. Baroreflex curves were generated by inflation of implanted hydraulic occluders on the vena cava and aortic arch or by administration of phenylephrine and sodium nitroprusside. Experiments were carried out before and after intravenous administration of the AT1 antagonist L-158,809. Rabbits with heart failure exhibited significantly lower arterial pressure (81 +/- 3 vs. 69 +/- 4 mmHg, P < 0.05), elevated resting HR (230 +/- 5 vs. 260 +/- 10 beats/min, P < 0.05), and elevated left atrial pressure (3.6 +/- 0.7 vs. 13.1 +/- 0.7 mmHg, P < 0.05). ANG II blockade had little effect on resting or baroreflex parameters in normal rabbits. However, in rabbits with heart failure, L-158,809 enhanced baroreflex sensitivity (2.7 +/- 0.5 vs. 4.7 +/- 0.8 beats.min-1.mmHg-1; P < 0.05), primarily by increasing the minimum HR evoked during baroreceptor activation. beta 1-Blockade had no effect on any baroreflex parameter after L-158,809 in rabbits with heart failure. However, L-158,809 significantly reduced the minimum HR after pretreatment with atropine in rabbits with heart failure. These data suggest that ANG II plays a role in modulation of cardiac sympathetic tone in this model of heart failure and may be responsible for the depressed baroreflex sensitivity observed in heart failure.

Baroreflex modulation by angiotensins at the rat rostral and caudal ventrolateral medulla

2006 ◽  
Vol 290 (4) ◽  
pp. R1027-R1034 ◽  
Author(s):  
Andréia C. Alzamora ◽  
Robson A. S. Santos ◽  
Maria J. Campagnole-Santos
Keyword(s):  
Heart Rate ◽  
Baroreflex Sensitivity ◽  
Opposite Effect ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Differential Modulation ◽  
Baroreflex Control ◽  
Caudal Ventrolateral Medulla ◽  
Angiotensin Peptides ◽  
Reflex Bradycardia

We determined the effect of microinjection of ANG-(1–7) and ANG II into two key regions of the medulla that control the circulation [rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively)] on baroreflex control of heart rate (HR) in anesthetized rats. Reflex bradycardia and tachycardia were induced by increases and decreases in mean arterial pressure produced by intravenous phenylephrine and sodium nitroprusside, respectively. The pressor effects of ANG-(1–7) and ANG II (25 pmol) after RVLM microinjection (11 ± 0.8 and 10 ± 2 mmHg, respectively) were not accompanied by consistent changes in HR. In addition, RVLM microinjection of these angiotensin peptides did not alter the bradycardic or tachycardic component of the baroreflex. CVLM microinjections of ANG-(1–7) and ANG II produced hypotension (−11 ± 1.5 and −11 ± 1.9 mmHg, respectively) that was similarly not accompanied by significant changes in HR. However, CVLM microinjections of angiotensins induced differential changes in the baroreflex control of HR. ANG-(1–7) attenuated the baroreflex bradycardia (0.26 ± 0.06 ms/mmHg vs. 0.42 ± 0.08 ms/mmHg before treatment) and facilitated the baroreflex tachycardia (0.86 ± 0.19 ms/mmHg vs. 0.42 ± 0.10 ms/mmHg before treatment); ANG II produced the opposite effect, attenuating baroreflex tachycardia (0.09 ± 0.06 ms/mmHg vs. 0.31 ± 0.07 ms/mmHg before treatment) and facilitating the baroreflex bradycardia (0.67 ± 0.16 ms/mmHg vs. 0.41 ± 0.05 ms/mmHg before treatment). The modulatory effect of ANG II and ANG-(1–7) on baroreflex sensitivity was completely abolished by peripheral administration of methylatropine. These results suggest that ANG II and ANG-(1–7) at the CVLM produce a differential modulation of the baroreflex control of HR, probably through distinct effects on the parasympathetic drive to the heart.

Mechanisms of hypertension in transgenic rats expressing the mouse Ren-2 gene

1994 ◽  
Vol 266 (4) ◽  
pp. R1273-R1279 ◽  
Author(s):  
A. Moriguchi ◽  
K. B. Brosnihan ◽  
H. Kumagai ◽  
D. Ganten ◽  
C. M. Ferrario
Keyword(s):  
Mature Female ◽  
Response To Therapy ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Transgenic Rats ◽  
Contrast Administration ◽  
Systemic Injection ◽  
Endothelin 1 ◽  
Sd Rats ◽  
Insight Into

Transgenic (TG) rats carrying the mouse Ren-2 gene (Ren-2d)27 are a newly established monogenetic model in hypertension research. To gain an insight into the mechanisms of this form of hypertension we determined the effects of a 13-day therapy with losartan (10 mg/kg) or lisinopril (20 mg/kg) on the blood pressure (BP) and plasma levels of angiotensin (ANG) peptides of mature female TG hypertensive and Sprague-Dawley (SD) rats. The contribution of endothelium-derived nitric oxide (NO) to the maintenance of their hypertension and the response to therapy was evaluated by systemic injection of either NG-monomethyl-L-arginine (L-NMMA) or endothelin-1. Hypertension in TG rats was associated with decreased plasma ANG I, no differences in plasma ANG II, and plasma ANG-(1-7) near the detectable level. Lisinopril lowered BP more than losartan in both TG hypertensive and normotensive controls. In both strains, the chronic fall in BP produced by lisinopril was accompanied by significant increases in plasma ANG I and ANG-(1-7), while losartan augmented plasma ANG I and ANG II in both strains and plasma ANG-(1-7) in TG rats. Inhibition of NO synthase reversed the fall in BP produced by either lisinopril or losartan in SD controls. In contrast, administration of L-NMMA to TG rats given the same therapy did not. The transient endothelium-mediated relaxing phase of the depressor response to systemic injections of endothelin-1 was attenuated by losartan and lisinopril in TG rats. These studies indicate that hypertension in female TG rats is mediated by the RAS.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Improved cardiovascular autonomic modulation in transgenic rats expressing an Ang-(1-7)-producing fusion protein

2017 ◽  
Vol 95 (9) ◽  
pp. 993-998 ◽  
Author(s):  
Daniela Ravizzoni Dartora ◽  
Maria-Claudia Irigoyen ◽  
Karina Rabello Casali ◽  
Ivana C. Moraes-Silva ◽  
Mariane Bertagnolli ◽  
...  
Keyword(s):  
Heart Rate ◽  
Cardiovascular Effects ◽  
Chronic Administration ◽  
Acute Administration ◽  
Autonomic Modulation ◽  
Sprague Dawley ◽  
Transgenic Rats ◽  
Sd Rats ◽  
Sympathetic Modulation ◽  
Acute Elevation

Angiotensin-(1-7) counterbalances angiotensin II cardiovascular effects. However, it has yet to be determined how cardiovascular autonomic modulation may be affected by chronic and acute elevation of Ang-(1-7). Hemodynamics and cardiovascular autonomic profile were evaluated in male Sprague-Dawley (SD) rats and transgenic rats (TGR) overexpressing Ang-(1-7) [TGR(A1-7)3292]. Blood pressure (BP) was directly measured while cardiovascular autonomic modulation was evaluated by spectral analysis. TGR received A-779 or vehicle and SD rats received Ang-(1-7) or vehicle and were monitored for 5 h after i.v. administration. In another set of experiments with TGR, A-779 was infused for 7 days using osmotic mini pumps. Although at baseline no differences were observed, acute administration of A-779 in TGR produced a marked long-lasting increase in BP accompanied by increased BP variability (BPV) and sympathetic modulation to the vessels. Likewise, chronic administration of A-779 with osmotic mini pumps in TGR increased heart rate, sympathovagal balance, BPV, and sympathetic modulation to the vessels. Administration of Ang-(1-7) to SD rats increased heart rate variability values in 88% accompanied by 8% of vagal modulation increase and 18% of mean BP reduction. These results show that both acute and chronic alteration in the Ang-(1-7)-Mas receptor axis may lead to important changes in the autonomic control of circulation, impacting either sympathetic and (or) parasympathetic systems.

Estrogen enhances baroreflex control of heart rate in conscious ovariectomized rats

1998 ◽  
Vol 76 (4) ◽  
pp. 381-386 ◽  
Author(s):  
Mahmoud M El-Mas ◽  
Abdel A Abdel-Rahman
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Baroreflex Sensitivity ◽  
Female Rats ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Sprague Dawley ◽  
Baroreflex Control ◽  
Baroreflex Function ◽  
Vehicle Treatment

In previous studies, we have shown that the baroreflex control of heart rate is significantly attenuated in females compared with age-matched males. This study investigated the role of estrogen in the modulation of baroreflex function in conscious unrestrained rats. Baroreflex-mediated decreases in heart rate in response to increments in blood pressure evoked by phenylephrine were evaluated in conscious freely moving male and female Sprague-Dawley rats as well as in ovariectomized rats. The effect of a 2-day 17 beta -estradiol (50 µg ·kg-1 ·day-1, s.c.) or vehicle treatment on baroreflex sensitivity was investigated in ovariectomized rats. Intravenous bolus doses of phenylephrine (1-16 µg/kg) elicited dose-dependent pressor and bradycardic responses in all groups of rats. Regression analysis of the baroreflex curves relating increments in blood pressure to the associated heart rate responses revealed a significantly (p < 0.05) smaller baroreflex sensitivity in female compared with male rats (-1.22 ± 0.07 and -1.85 ± 0.15 beats ·min-1 ·mmHg-1, respectively), suggesting an attenuated baroreflex function in females. In age-matched ovariectomized rats, baroreflex sensitivity showed further reduction (-0.93 ± 0.02 beats ·min-1 ·mmHg-1). Treatment of ovariectomized rats with 17 beta -estradiol significantly (p < 0.05) enhanced the baroreflex sensitivity (-1.41 ± 0.16 beats ·min-1 ·mmHg-1) to a level that was slightly higher than that of sham-operated female rats. Furthermore, baroreflex sensitivity of ovariectomized estradiol-treated rats was not significantly different from that of age-matched male rats. The vehicle, on the other hand, had no effect on baroreflex sensitivity of ovariectomized rats. These data support our earlier findings that sexual dimorphism exists in baroreflex control of heart rate. More importantly, the present study provides experimental evidence that suggests a facilitatory role for estrogen in the modulation of baroreflex function.Key words: rat, gender, baroreflex sensitivity, 17 beta -estradiol, ovariectomy.

scholarly journals Combined Suppression of the Intrarenal and Circulating Vasoconstrictor Renin-ACE-ANG II Axis and Augmentation of the Vasodilator ACE2-ANG 1-7-Mas Axis Attenuates the Systemic Hypertension in Ren-2 Transgenic Rats Exposed to Chronic Hypoxia

2015 ◽  
pp. 11-24 ◽  
Author(s):  
L. ČERVENKA ◽  
J. BÍBOVÁ ◽  
Z. HUSKOVÁ ◽  
Z. VAŇOURKOVÁ ◽  
H. J. KRAMER ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Hypoxia ◽  
Substantial Reduction ◽  
Kidney Tissue ◽  
Renin Angiotensin System ◽  
Systemic Hypertension ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Transgenic Rats ◽  
Pressure Lowering

The aim of the present study was to test the hypothesis that chronic hypoxia would aggravate hypertension in Ren-2 transgenic rats (TGR), a well-defined monogenetic model of hypertension with increased activity of endogenous renin-angiotensin system (RAS). Systolic blood pressure (SBP) in conscious rats and mean arterial pressure (MAP) in anesthetized TGR and normotensive Hannover Sprague-Dawley (HanSD) rats were determined under normoxia that was either continuous or interrupted by two weeks´ hypoxia. Expression, activities and concentrations of individual components of RAS were studied in plasma and kidney of TGR and HanSD rats under normoxic conditions and after exposure to chronic hypoxia. In HanSD rats two weeks´ exposure to chronic hypoxia did not alter SBP and MAP. Surprisingly, in TGR it decreased markedly SBP and MAP; this was associated with substantial reduction in plasma and kidney renin activities and also of angiotensin II (ANG II) levels, without altering angiotensin-converting enzyme (ACE) activities. Simultaneously, in TGR the exposure to hypoxia increased kidney ACE type 2 (ACE2) activity and angiotensin 1-7 (ANG 1-7) concentrations as compared with TGR under continuous normoxia. Based on these results, we propose that suppression of the hypertensiogenic ACE-ANG II axis in the circulation and kidney tissue, combined with augmentation of the intrarenal vasodilator ACE2-ANG 1-7 axis, is the main mechanism responsible for the blood pressure-lowering effects of chronic hypoxia in TGR.

Abstract MP04: Cardiac ACE2/Angiotensin-(1-7) in Rats Expressing Human Angiotensinogen Gene

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Jasmina Varagic ◽  
Jessica VonCannon ◽  
Sarfaraz Ahmad ◽  
Michael Bader ◽  
Carlos M Ferrario
Keyword(s):  
Cardiac Hypertrophy ◽  
Cardiac Tissue ◽  
Male Rats ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Transgenic Rats ◽  
Sd Rats ◽  
Agt Gene ◽  
Tissue Angiotensin

When compared to Sprague Dawley (SD) control rats, transgenic rats expressing the human angiotensinogen (AGT) gene [TGR(hAGT)L1623] exhibit hypertension associated with cardiac hypertrophy and higher cardiac tissue angiotensin (Ang) II. Whether the hypertension and cardiac hypertrophy in these rats expressing the human AGT are related to a non-canonical pathway for Ang II formation or suppression of the counter regulatory mechanism mediated by ACE2 and Ang-(1-7) has not been established. Consequently, cardiac peptides were determined by RIA in 9 [TGR(hAGT)L1623] and 11 SD male rats (17 weeks of age). ACE2 activities in homogenized heart tissues were determined by HPLC. Cardiac Ang II content was four times higher (37.05 ± 5.04 vs. 9.62 ± 0.93 fmol/mg protein; p <0.0001) while the Ang-(1-7) level increased only 1.3 times (18.02 ± 1.62 vs 13.37 ± 1.74 fmol/mg protein; p=0.06) in TGR(hAGT)L1623 rats when compared with SD rats. Although, the Ang II/Ang-(1-7) ratio was higher in transgenic rats harboring the human AGT gene (2.10 ± 0.27 vs 0.90 ± 0.19; p <0.005), ACE2 activities between these two strains of animals were not different (12.21 ± 0.76 vs. 10.80 ± 0.91 fmol/min/mg; p >0.05). Since human AGT protein is not cleaved by rat renin, our data continues to support the view that hypertension and cardiac hypertrophy in this transgenic strain are induced by activation of a non-renin mechanism rather than a primary suppression of the compensatory Ang II degrading pathway mediated by ACE2. Further studies are necessary to determine the role of enzymes affecting Ang-(1-7) metabolism in the observed inadequate balance between Ang II and Ang-(1-7).

scholarly journals Angiotensin peptides acting at rostral ventrolateral medulla contribute to hypertension of TGR(mREN2)27 rats

2000 ◽  
Vol 2 (3) ◽  
pp. 137-142 ◽  
Author(s):  
MARCO A. P. FONTES ◽  
OVIDIU BALTATU ◽  
SORDAINI M. CALIGIORNE ◽  
MARIA J. CAMPAGNOLE-SANTOS ◽  
DETLEV GANTEN ◽  
...  
Keyword(s):  
Hypotensive Effect ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Transgenic Rats ◽  
Conscious Rats ◽  
Significant Fall ◽  
Angiotensin Peptides ◽  
Sd Rats

Fontes, Marco A. P., Ovidiu Baltatu, Sordaini M. Caligiorne, Maria J. Campagnole-Santos, Detlev Ganten, Michael Bader, and Robson A. S. Santos. Angiotensin peptides acting at rostral ventrolateral medulla contribute to hypertension of TGR(mREN2)27 rats. Physiol Genomics 2: 137–142, 2000.—We have previously demonstrated that microinjections of the selective angiotensin-( 1 – 7 ) [ANG-( 1 – 7 )] antagonist, A-779, into the rostral ventrolateral medulla (RVLM) produces a significant fall in mean arterial pressure (MAP) and heart rate (HR) in both anesthetized and conscious rats. In contrast, microinjection of angiotensin II (ANG II) AT1 receptor antagonists did not change MAP in anesthetized rats and produced dose-dependent increases in MAP when microinjected into the RVLM of conscious rats. In the present study, we evaluated whether endogenous ANG-( 1 – 7 ) and ANG II acting at the RVLM contribute to the hypertension of transgenic rats harboring the mouse renin Ren-2 gene, TGR(mREN2)27. Unilateral microinjection of A-779 (0.1 nmol) produced a significant fall in MAP (−25 ± 5 mmHg) and HR (−57 ± 20 beats/min) of awake TGR rats. The hypotensive effect was greater than that observed in Sprague-Dawley (SD) rats (−9 ± 2 mmHg). Microinjection of the AT1 antagonist CV-11974 (0.2 nmol) produced a fall in MAP in TGR rats (−14 ± 4 mmHg), contrasting with the pressor effect observed in SD rats (33 ± 9 mmHg). These results indicate that endogenous ANG-( 1 – 7 ) exerts a significant pressor action in the RVLM, contributing to the hypertension of TGR(mREN2)27 transgenic rats. The role of ANG II at the RVLM seems to be dependent on its endogenous level in this area.

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