Endothelial vasoconstrictor prostanoids modulate contractions to acetylcholine and ANG II in Ren-2 rats

1997 ◽  
Vol 272 (1) ◽  
pp. H493-H500 ◽  
Author(s):  
G. Noll ◽  
M. G. Lang ◽  
M. R. Tschudi ◽  
D. Ganten ◽  
T. F. Luscher
Keyword(s):  
Angiotensin Ii ◽  
Vascular Function ◽  
Tissue Perfusion ◽  
Isometric Tension ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Angiotensin I ◽  
Transgenic Rats ◽  
Endothelin 1 ◽  
Thromboxane Receptor Antagonist

We investigated vascular function in mouse Ren-2 transgenic rats with hypertension. Mesenteric resistance arteries of transgenic and Sprague-Dawley rats (controls) were isolated at ages 6 and 12 wk and suspended in myographs for isometric tension recording. Systolic blood pressure was higher in transgenic than control rats (P < 0.05). Contractions to norepinephrine and endothelin-1 were comparable in transgenic and control rats, but the sensitivity decreased with age in both strains (P < 0.05). Contractions to angiotensin I were comparable in 6-wk-old transgenic rats and controls, but the response to angiotensin I was more pronounced in transgenic rats at 12 wk of age. Contractions to angiotensin II were higher in transgenic rats and decreased with age in both strains. Preincubation with the cyclooxygenase inhibitor meclofenamate or the thromboxane receptor antagonist SQ-30741 blunted the response only in 6-wk-old transgenic rats. In quiescent vascular rings, acetylcholine evoked endothelium-dependent contractions after inhibition of nitric oxide formation by N omega-nitro-L-arginine methyl ester only in transgenic rats. These contractions were inhibited by SQ-30741 (P < 0.05) but not by the thromboxane synthase inhibitor CGS-13080. Contractions to the thromboxane analogue U-46619 were comparable in both strains at the age of 6 wk; sensitivity was increased in transgenic rats at 12 wk (P < 0.05). In conclusion, in mesenteric resistance arteries of Ren-2 transgenic rats I) contractions to angiotensin I and II but not to norepinephrine and endothelin-1 are increased, and 2) acetylcholine as well as angiotensin II modulate endothelium-dependent contractions mediated by prostaglandin H2. These alterations together with increased sensitivity to thromboxane could contribute to maintenance as well as to impaired tissue perfusion of this form of hypertension.

Embryonic lethality in Dear gene-deficient mice: new player in angiogenesis

2005 ◽  
Vol 23 (3) ◽  
pp. 257-268 ◽  
Author(s):  
Victoria L. M. Herrera ◽  
Lorenz R. B. Ponce ◽  
Pia D. Bagamasbad ◽  
Benjamin D. VanPelt ◽  
Tamara Didishvili ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Embryonic Lethality ◽  
Female Rats ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Angiotensin Ii Receptor ◽  
Endothelin 1 ◽  
Receptor Isoforms ◽  
Age Range ◽  
Deficient Mice

The dual endothelin-1/angiotensin II receptor (Dear) binds endothelin-1 (ET-1) and angiotensin II (ANG II) with equal affinities in the Dahl S/JRHS rat strain. To elucidate its physiological significance within the context of multiple receptor isoforms and diverse ET-1 and ANG II functions spanning blood pressure regulation, tumor proliferation, and angiogenesis, we characterized mouse Dear and Dear-deficient mice. Unlike null mutant models of ET-1, ANG II, and all other ET-1 and ANG II receptors, Dear−/− deficiency results in impaired angiogenesis, dysregulated neuroepithelial development, and embryonic lethality by embryonic day 12.5. Interestingly, mouse Dear does not bind ANG II, similar to Dahl R/JRHS rat Dear, but binds ET-1 and vascular endothelial growth factor (VEGF) signal peptide (VEGFsp) with equal affinities, suggesting a putative novel multifunction for VEGFsp and a parsimonious mechanism for coordination of VEGF-induced and Dear-mediated pathways. Consistent with its developmental angiogenic role, Dear inhibition results in decreased tumor growth in B16-F10 melanoma cell-induced subcutaneous tumor in female Dear+/−/C57BL6BC10 mice, but not in males (age 3.5 mo), and in 127Cs radiation-induced orthotopic mammary tumors in Sprague-Dawley female rats (age range 3–6.5 mo). Altogether, the data identify Dear as a new player in angiogenesis during development downstream to, and nonredundant with, VEGF-mediated pathways, as well as a putative modulator of tumor angiogenesis acting within a gender-specific paradigm.

Effect of increased potassium intake on the renin–angiotensin–aldosterone system and subcutaneous resistance arteries: a randomized crossover study

2020 ◽  
Author(s):  
Rasmus Dreier ◽  
Bahareh Abdolalizadeh ◽  
Camilla L Asferg ◽  
Lisbet R Hölmich ◽  
Niels H Buus ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Crossover Study ◽  
Vascular Function ◽  
Plasma Concentrations ◽  
Resistance Arteries ◽  
Renin Angiotensin Aldosterone System ◽  
Potassium Supplement ◽  
Renin Angiotensin ◽  
Potassium Intake ◽  
Urinary Potassium

Abstract Background Increased potassium intake lowers blood pressure (BP) in hypertensive patients. The underlying mechanism is not fully understood but must be complex because increased potassium intake elevates circulating concentrations of the BP-raising hormone aldosterone. Methods In a randomized placebo-controlled crossover study in 25 normotensive men, we investigated the effect of 4 weeks of potassium supplement (90 mmol/day) compared with 4 weeks of placebo on the renin–angiotensin–aldosterone system (RAAS), urine composition and 24-h ambulatory BP. Vascular function was also assessed through wire myograph experiments on subcutaneous resistance arteries from gluteal fat biopsies. Results Higher potassium intake increased urinary potassium excretion (144.7 ± 28.7 versus 67.5 ± 25.5 mmol/24-h; P &lt; 0.0001) and plasma concentrations of potassium (4.3 ± 0.2 versus 4.0 ± 0.2 mmol/L; P = 0.0002), renin {mean 16 [95% confidence interval (CI) 12–23] versus 11 [5–16] mIU/L; P = 0.0047}, angiotensin II [mean 10.0 (95% CI 6.2–13.0) versus 6.1 (4.0–10.0) pmol/L; P = 0.0025] and aldosterone [mean 440 (95% CI 336–521) versus 237 (173–386) pmol/L; P &lt; 0.0001]. Despite RAAS activation, systolic BP (117.6 ± 5.8 versus 118.2 ± 5.2 mmHg; P = 0.48) and diastolic BP (70.8 ± 6.2 versus 70.8 ± 6.3 mmHg; P = 0.97) were unchanged. In the wire myograph experiments, higher potassium intake did not affect endothelial function as assessed by acetylcholine [logarithmically transformed half maximal effective concentration (pEC50): 7.66 ± 0.95 versus 7.59 ± 0.85; P = 0.86] and substance P (pEC50: 8.42 ± 0.77 versus 8.41 ± 0.89; P = 0.97) or vascular smooth muscle cell reactivity as assessed by angiotensin II (pEC50: 9.01 ± 0.86 versus 9.02 ± 0.59; P = 0.93) and sodium nitroprusside (pEC50: 7.85 ± 1.07 versus 8.25 ± 1.32; P = 0.25) but attenuated the vasodilatory response of retigabine (pEC50: 7.47 ± 1.16 versus 8.14 ± 0.90; P = 0.0084), an activator of Kv7 channels. Conclusions Four weeks of increased potassium intake activates the RAAS in normotensive men without changing BP and this is not explained by improved vasodilatory responses ex vivo.

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 Renal autoregulation and passive pressure-flow relationships in diabetes and hypertension

2010 ◽  
Vol 299 (4) ◽  
pp. F837-F844 ◽  
Author(s):  
J. V. Hill ◽  
G. Findon ◽  
R. J. Appelhoff ◽  
Z. H. Endre
Keyword(s):  
Angiotensin Ii ◽  
Creatinine Clearance ◽  
Vascular Function ◽  
Sprague Dawley ◽  
Pressure Flow ◽  
Sd Rats ◽  
Pressure Threshold ◽  
Renal Flow ◽  
Renal Vascular

We investigated renal hemodynamics in isolated, perfused kidneys from rat models of diabetes and hypertension. Autoregulation and passive vascular responses were measured using stepped pressure ramps in the presence of angiotensin II (pEC50) or papaverine (0.1 mM), respectively. Male diabetic heterozygote m(Ren2)27 rats were compared with three male control groups: nondiabetic, normotensive Sprague-Dawley (SD) rats; nondiabetic, hypertensive heterozygote m(Ren2)27 rats; and diabetic, normotensive SD rats. Kidney function (proteinuria, creatinine clearance) was monitored before induction and at monthly intervals. Vascular function was measured in vitro in rats of induction age (6–8 wk) and at 2 and 4 mo postinduction. Renal flow correlated with age, but not diabetes or the Ren2 gene. Kidney weight-specific and body weight-specific renal flow differed between diabetic and nondiabetic rats because diabetic rats had higher kidney but lower body weights. Kidneys from all groups showed effective autoregulation in the presence of angiotensin II. The autoregulatory pressure threshold of m(Ren2)27 rats was higher, and the autoregulation pressure range was wider, compared with SD rats. When vascular smooth muscle activity was blocked with papaverine, pressure-flow responses differed between groups and with time. The m(Ren2)27 rat groups showed higher renal vascular resistance at lower pressures, suggesting greater vascular stiffness. In contrast, diabetic SD rat kidneys demonstrated reduced vessel stiffness. Flow was impaired in diabetic m(Ren2)27 rats at 4 mo, and this correlated with a decline in creatinine clearance. The results suggest that the characteristic late decline in renal filtration function in diabetes- and hypertension-related renal disease follows changes in renal vascular compliance.

scholarly journals The Functional and Structural Changes in the Basilar Artery Due to Overpressure Blast Injury

2015 ◽  
Vol 35 (12) ◽  
pp. 1950-1956 ◽  
Author(s):  
Hale Z Toklu ◽  
Judy Muller-Delp ◽  
Zhihui Yang ◽  
Şehkar Oktay ◽  
Yasemin Sakarya ◽  
...  
Keyword(s):  
Basilar Artery ◽  
Vascular Function ◽  
Structural Changes ◽  
Sprague Dawley ◽  
Endothelin 1 ◽  
Msec Duration ◽  
Basilar Arteries ◽  
Wave Induced ◽  
Endothelial Nitric Oxide ◽  
Cerebral Vascular

Overpressure blast-wave induced brain injury (OBI) leads to progressive pathophysiologic changes resulting in a reduction in brain blood flow, blood brain barrier breakdown, edema, and cerebral ischemia. The aim of this study was to evaluate cerebral vascular function after single and repeated OBI. Male Sprague-Dawley rats were divided into three groups: Control (Naive), single OBI (30 psi peak pressure, 1 to 2 msec duration), and repeated (days 1, 4, and 7) OBI (r-OBI). Rats were killed 24 hours after injury and the basilar artery was isolated, cannulated, and pressurized (90 cm H2O). Vascular responses to potassium chloride (KCl) (30 to 100 mmol/L), endothelin-1 (10−12 to 10−7 mol/L), acetylcholine (ACh) (10−10 to 10−4 mol/L) and diethylamine-NONO-ate (DEA-NONO-ate) (10−10 to 10−4 mol/L) were evaluated. The OBI resulted in an increase in the contractile responses to endothelin and a decrease in the relaxant responses to ACh in both single and r-OBI groups. However, impaired DEA-NONO-ate-induced vasodilation and increased wall thickness to lumen ratio were observed only in the r-OBI group. The endothelin-1 type A (ETA) receptor and endothelial nitric oxide synthase (eNOS) immunoreactivity were significantly enhanced by OBI. These findings indicate that both single and r-OBI impairs cerebral vascular endothelium-dependent dilation, potentially a consequence of endothelial dysfunction and/or vascular remodelling in basilar arteries after OBI.

Effect of removal of adventitia on vascular smooth muscle contraction and relaxation

2001 ◽  
Vol 280 (6) ◽  
pp. H2876-H2881 ◽  
Author(s):  
M. C. González ◽  
S. M. Arribas ◽  
F. Molero ◽  
M. S. Fernández-Alfonso
Keyword(s):  
Vascular Function ◽  
Smooth Muscle Contraction ◽  
Isometric Tension ◽  
Organ Bath ◽  
Sprague Dawley ◽  
Iliac Arteries ◽  
Sprague Dawley Rats ◽  
The Media ◽  
Vascular Smooth Muscle Contraction ◽  
Contraction And Relaxation

The aim of the present study was to determine whether the adventitia of large arteries modulates vascular function. We developed a method to obtain functional vascular rings devoid of adventitia. Carotid and iliac arteries from 3-mo-old Sprague-Dawley rats were denuded from adventitia after treatment with collagenase followed by gentle peeling. Adventitia removal and integrity of the media was demonstrated by optical and confocal microscopy. Arterial rings with or without adventitia and with or without endothelium were mounted in an organ bath for isometric tension recording. Responses to 75 mM KCl or norepinephrine (0.1 nM–1 μM) were significantly reduced in segments without adventitia. Acetylcholine-induced relaxation (0.1 μM–0.1 mM) was enhanced in arteries without adventitia, whereas sodium nitroprusside-induced responses were not modified. These results demonstrate that the combination of stripping with a previous collagenase treatment allows us to obtain functional rings devoid of adventitia and that this layer plays a role in contractile capacity and in endothelium-modulated responses.

scholarly journals Vascular function in rats with adenine-induced chronic renal failure

2012 ◽  
Vol 302 (12) ◽  
pp. R1426-R1435 ◽  
Author(s):  
Lisa Nguy ◽  
Holger Nilsson ◽  
Jaana Lundgren ◽  
Maria E. Johansson ◽  
Tom Teerlink ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Vascular Function ◽  
Ex Vivo ◽  
Mesenteric Arteries ◽  
Maximal Response ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Severe Renal Failure ◽  
Stress Markers

The aim of the present study was to characterize the function of resistance arteries, and the aorta, in rats with adenine-induced chronic renal failure (A-CRF). Sprague-Dawley rats were randomized to chow with or without adenine supplementation. After 6–10 wk, mesenteric arteries and thoracic aortas were analyzed ex vivo by wire myography. Plasma creatinine concentrations were elevated twofold at 2 wk, and eight-fold at the time of death in A-CRF animals. Ambulatory systolic and diastolic blood pressures measured by radiotelemetry were significantly elevated in A-CRF animals from week 3 and onward. At death, A-CRF animals had anemia, hyperphosphatemia, hyperparathyroidism, and elevated plasma levels of asymmetric dimethylarginine and oxidative stress markers. There were no significant differences between groups in the sensitivity, or maximal response, to ACh, sodium nitroprusside (SNP), norepinephrine, or phenylephrine in either mesenteric arteries or aortas. However, in A-CRF animals, the rate of aortic relaxation was significantly reduced following washout of KCl (both in intact and endothelium-denuded aorta) and in response to ACh and SNP. Also the rate of contraction in response to KCl was significantly reduced in A-CRF animals both in mesenteric arteries and aortas. The media of A-CRF aortas was thickened and showed focal areas of fragmented elastic lamellae and disorganized smooth muscle cells. No vascular calcifications could be detected. These results indicate that severe renal failure for a duration of less than 10 wk in this model primarily affects the aorta and mainly slows the rate of relaxation.

Proximal tubular fluid, kidney, and plasma levels of angiotensin II in hypertensive ren-2 transgenic rats

1997 ◽  
Vol 273 (2) ◽  
pp. F246-F253 ◽  
Author(s):  
K. D. Mitchell ◽  
S. M. Jacinto ◽  
J. J. Mullins
Keyword(s):  
Left Kidney ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Angiotensin I ◽  
Transgenic Rats ◽  
A Value ◽  
Sprague Dawley Rats ◽  
Proximal Tubular ◽  
Fluid Collections ◽  
Normotensive Control

The present study was performed to assess the plasma and kidney levels of angiotensin I (ANG I) and ANG II during prehypertensive (4- to 5-wk old), development (6- to 8-wk old), and maintenance (10- to 12-wk old) phases of hypertension in pentobarbital-anesthetized transgenic rats [TGR; strain name: TGR(mRen2)27] and age-matched transgene-negative Hannover Sprague-Dawley rats (HanSD). At 4-5 wk, mean arterial pressures of TGR were not different from those of HanSD (110 +/- 5 vs. 114 +/- 4 mmHg). However, mean arterial pressures of 6-8 wk and 10-12 wk TGR were higher than those of HanSD (179 +/- 3 vs. 110 +/- 6 and 173 +/- 5 vs. 116 +/- 3 mmHg, respectively; P < 0.01 in both cases). Plasma ANG II levels in 4-5 wk and 6-8 wk TGR were not different from those in HanSD (70 +/- 11 vs. 66 +/- 7 and 60 +/- 8 vs. 48 +/- 12 fmol/ml, respectively). However, plasma ANG II levels in 10-12 wk TGR were higher than those in HanSD (125 +/- 26 vs. 38 +/- 12 fmol/ml, P < 0.01). Kidney ANG II levels in 4-5 wk, 6-8 wk, and 10-12 wk TGR averaged 370 +/- 57, 247 +/- 16, and 562 +/- 86 fmol/g, respectively, values not different from those in HanSD. In additional studies performed on 6-8 wk TGR and HanSD, multiple free-flow proximal tubular fluid collections were obtained and pooled for each animal. In these experiments, mean arterial pressures of the 10 TGR and 7 HanSD studied averaged 178 +/- 9 and 129 +/- 3 mmHg (P < 0.01), respectively. The ANG II concentration in proximal tubular fluid obtained from TGR averaged 5.6 +/- 2.1 pmol/ml (n = 10), a value not different from that in proximal tubular fluid collected from HanSD (5.3 +/- 2.8 pmol/ml, n = 7). However, the ANG II contents of the micropunctured left kidney and the nonmicropunctured right kidney of TGR were lower than those in HanSD (690 +/- 95 vs. 1,374 +/- 210 and 659 +/- 119 vs. 1,303 +/- 196 fmol/g, respectively; P < 0.01 in both cases). The present findings indicate that proximal tubular fluid of hypertensive TGR contains nanomolar concentrations of ANG II and that proximal tubular fluid, plasma and kidney ANG II levels in anesthetized hypertensive TGR are not markedly suppressed compared with those in normotensive control rats.

Enalapril attenuates endothelin-1-induced hypertension via increased kinin survival

2003 ◽  
Vol 284 (6) ◽  
pp. H1899-H1903 ◽  
Author(s):  
Ahmed A. Elmarakby ◽  
Peter Morsing ◽  
David M. Pollock
Keyword(s):  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Neutral Endopeptidase ◽  
Sprague Dawley ◽  
Angiotensin Ii Receptor ◽  
Angiotensin Ii Receptor Antagonist ◽  
Endothelin 1 ◽  
Sprague Dawley Rats ◽  
Vasodilator Activity ◽  
Induced Hypertension

Recent studies have shown that angiotensin-converting enzyme (ACE) inhibitors attenuate endothelin-1 (ET-1)-induced hypertension, but the mechanisms for this effect have not been clarified. Initial experiments were conducted to contrast the effect of the ACE inhibitor enalapril, the combined ACE-neutral endopeptidase inhibitor omapatrilat, and the angiotensin II receptor antagonist candesartan on the hypertensive and renal response to ET-1 in anesthetized Sprague-Dawley rats. Acute intravenous infusion of ET-1 (10 pmol · kg−1 · min−1) for 60 min significantly increased mean arterial pressure (MAP) from 125 ± 8 to 145 ± 8 mmHg ( P < 0.05) and significantly decreased glomerular filtration rate (GFR) from 0.31 ± 0.09 to 0.13 ± 0.05 ml · min−1 · 100 g kidney wt−1. Pretreatment with enalapril (10 mg/kg iv) before ET-1 infusion inhibited the increase in MAP (121 ± 4 vs. 126 ± 4 mmHg) before and during ET-1 infusion, respectively ( P < 0.05) without blocking the effect of ET-1 on GFR. In contrast, neither omapatrilat (30 mg/kg) nor candesartan (10 mg/kg) had any effect on ET-1-induced increases in MAP or decreases in GFR. To determine whether the effect of enalapril was due to the decrease in angiotensin II or increase in kinin formation, rats were given REF-000359 (1 mg/kg iv), a selective B2 receptor antagonist, with or without enalapril before ET-1 infusion. REF-000359 completely blocked the effect of enalapril on ET-1 infusion (MAP was 117 ± 5 vs. 135 ± 5 mmHg before and during ET-1 infusion, respectively, P < 0.05). REF-000359 alone had no effect on the response to ET-1 infusion (MAP was 117 ± 4 vs. 144 ± 4 mmHg before and during ET-1 infusion, respectively, P < 0.05). REF-000359 with or without enalapril had no significant effect on the ability of ET-1 infusion to decrease GFR. These findings support the hypothesis that decreased catabolism of bradykinin and its subsequent vasodilator activity oppose the actions of ET-1 to increase MAP.

scholarly journals Hyperinsulinemic rats are normotensive but sensitized to angiotensin II

2008 ◽  
Vol 294 (4) ◽  
pp. R1240-R1247 ◽  
Author(s):  
Maria E. Johansson ◽  
Irene J. Andersson ◽  
Camilla Alexanderson ◽  
Ole Skøtt ◽  
Agneta Holmäng ◽  
...  
Keyword(s):  
Nervous System ◽  
Angiotensin Ii ◽  
Sympathetic Nervous System ◽  
Vascular Function ◽  
Ex Vivo ◽  
Sprague Dawley ◽  
Angiotensin Ii Receptor ◽  
Air Jet ◽  
Important Interaction ◽  
Sympathetic Nervous

The effect of insulin on blood pressure (BP) is debated, and an involvement of an activated renin-angiotensin aldosterone system (RAAS) has been suggested. We studied the effect of chronic insulin infusion on telemetry BP and assessed sympathetic activity and dependence of the RAAS. Female Sprague-Dawley rats received insulin (2 units/day, INS group, n = 12) or insulin combined with losartan (30 mg·kg−1·day−1, INS+LOS group, n = 10), the angiotensin II receptor antagonist, for 6 wk. Losartan-treated (LOS group, n = 10) and untreated rats served as controls ( n = 11). We used telemetry to measure BP and heart rate (HR), and acute ganglion blockade and air-jet stress to investigate possible control of BP by the sympathetic nervous system. In addition, we used myograph technique to study vascular function ex vivo. The INS and INS+LOS groups developed euglycemic hyperinsulinemia. Insulin did not affect BP but increased HR (27 beats/min on average). Ganglion blockade reduced mean arterial pressure (MAP) similarly in all groups. Air-jet stress did not increase sympathetic reactivity but rather revealed possible blunting of the stress response in hyperinsulinemia. Chronic losartan markedly reduced 24-h-MAP in the INS+LOS group (−38 ± 1 mmHg P < 0.001) compared with the LOS group (−18 ± 1 mmHg, P ≤ 0.05). While insulin did not affect vascular function per se, losartan improved endothelial function in the aorta of insulin-treated rats. Our results raise doubt regarding the role of hyperinsulinemia in hypertension. Moreover, we found no evidence that insulin affects sympathetic nervous system activity. However, chronic losartan treatment revealed an important interaction between insulin and RAAS in BP control.

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