scholarly journals PDGF-A expression correlates with blood pressure and remodeling in 1K1C hypertensive rat arteries

1999 ◽  
Vol 276 (6) ◽  
pp. H2159-H2167 ◽  
Author(s):  
Anca Dobrian ◽  
Suzanne S. Wade ◽  
Russell L. Prewitt
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Thoracic Aorta ◽  
Direct Effect ◽  
Fold Increase ◽  
Small Arteries ◽  
Wall Area ◽  
Femoral Arteries ◽  
Hypertensive Rat ◽  
A Chain

We previously demonstrated remodeling of large and small arteries in angiotensin II-treated rats, paralleled by an increased expression of platelet-derived growth factor (PDGF)-A chain mRNA in large arteries. Both remodeling and PDGF-A expression were associated with elevation of blood pressure rather than a direct effect of angiotensin II. To further delineate the role of PDGF-A and elevated blood pressure, we assessed the level of PDGF-A and -B mRNA and protein in the wall of large as well as small arteries in the one-kidney, one-clip (1K1C) hypertensive rat, a non-renin-dependent model of hypertension. Fourteen days after renal artery stenosis, the thoracic aorta and both femoral arteries were collected from 1K1C rats ( n = 8) and uninephrectomized controls ( n = 8) and immediately processed for morphological measurement, immunohistochemistry, RT-PCR, and Western blotting. Systolic blood pressure was significantly elevated in hypertensive rats (202 ± 26 mmHg) compared with control rats (122 ± 7.9 mmHg) and was accompanied by arterial hypertrophy in both aorta and femoral arteries. The mRNA for PDGF-A chain was increased threefold in the thoracic aorta ( P < 0.05) of 1K1C rats, whereas the message for PDGF-B was not significantly changed in hypertensive versus control animals. A higher staining of the intima-media was observed by using an anti-PDGF-A chain polyclonal antibody on paraffin-embedded sections. Western blot results indicated an ∼2-fold increase in PDGF-A protein in aortic and femoral wall of the 1K1C rats. The results showed that both the mRNA and protein for PDGF-A chain are increased and well correlated with the blood pressure and wall area, suggesting a direct effect of elevated pressure on PDGF synthesis, which, in turn, may affect the onset and progression of vascular hypertrophy.

Angiotensin II-induced hypertrophy is potentiated in mice overexpressing p22phox in vascular smooth muscle

2005 ◽  
Vol 288 (1) ◽  
pp. H37-H42 ◽  
Author(s):  
David S. Weber ◽  
Petra Rocic ◽  
Adamantios M. Mellis ◽  
Karine Laude ◽  
Alicia N. Lyle ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
In Vivo Model ◽  
Ros Generation ◽  
Ang Ii ◽  
Vascular Hypertrophy ◽  
Wall Area

Increased reactive oxygen species (ROS) are implicated in several vascular pathologies associated with vascular smooth muscle hypertrophy. In the current studies, we utilized transgenic (Tg) mice (Tg p22smc) that overexpress the p22 phox subunit of NAD(P)H oxidase selectively in smooth muscle. These mice have a twofold increase in aortic p22 phox expression and H2O2 production and thus provide an excellent in vivo model in which to assess the effects of increased ROS generation on vascular smooth muscle cell (VSMC) function. We tested the hypothesis that overexpression of VSMC p22 phox potentiates angiotensin II (ANG II)-induced vascular hypertrophy. Male Tg p22smc mice and negative littermate controls were infused with either ANG II or saline for 13 days. Baseline blood pressure was not different between control and Tg p22smc mice. ANG II significantly increased blood pressure in both groups, with this increase being slightly exacerbated in the Tg p22smc mice. Baseline aortic wall thickness and cross-sectional wall area were not different between control and Tg p22smc mice. Importantly, the ANG II-induced increase in both parameters was significantly greater in the Tg p22smc mice compared with control mice. To confirm that this potentiation of vascular hypertrophy was due to increased ROS levels, additional groups of mice were coinfused with ebselen. This treatment prevented the exacerbation of hypertrophy in Tg p22smc mice receiving ANG II. These data suggest that although increased availability of NAD(P)H oxidase-derived ROS is not a sufficient stimulus for hypertrophy, it does potentiate ANG II-induced vascular hypertrophy, making ROS an excellent target for intervention aimed at reducing medial thickening in vivo.

The Effect of Captopril on Blood Pressure and Angiotensins I, II and III in Sodium-Depleted Dogs: Problems Associated with the Measurement of Angiotensin II after Inhibition of Converting Enzyme

1980 ◽  
Vol 58 (6) ◽  
pp. 445-450 ◽  
Author(s):  
J. J. Morton ◽  
M. Tree ◽  
J. Casals-Stenzel
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Fold Increase ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Active Inhibitor ◽  
Arterial Blood ◽  
Rapid Fall ◽  
Angiotensin Iii ◽  
Plasma Angiotensin

1. Changes in arterial blood pressure, blood angiotensin I, plasma angiotensin II and plasma angiotensin III were measured in conscious sodium—depleted dogs after infusion of captopril, an orally active inhibitor of converting enzyme. 2. Angiotensins II and III were measured after chromatography to remove angiotensin I, which increased in concentration after inhibition of converting enzyme and which interfered in the direct assay for angiotensin II. 3. Infusion of captopril at 20, 200, 2000 and 6000 μg h−1 kg−1, each for 3 h, produced a rapid fall in blood pressure and in concentration of angiotensin II. Angiotensin II was undetectable at 6000 μg h−1 kg−1 (mean pre-infusion value for all samples was 39 ± sd 15 pmol/I, n = 14) 4. The percentage fall in blood pressure correlated with the percentage fall in plasma angiotensin II (r = 0.65, P<0.001) 5. These results suggest that the initial fall in blood pressure may be mediated in part by the suppression of angiotensin II. 6. Blood angiotensin I concentration rose with each rate of infusion of drug to a maximum 16-fold increase at 6000 μg h−1 kg−1 (26−416 pmol/l). The rise in angiotensin I was inversely related to the fall in angiotensin II (r = −0.68, P<0.001)

Abstract P127: Angiotensin II Priming Enhances Prostaglandin E2 Vasoconstrictor Effects

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Maria P Kraemer ◽  
Fred Lamb ◽  
Richard M Breyer
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Area Under The Curve ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Ang Ii ◽  
Concentration Dependent Manner ◽  
Femoral Arteries

Prostaglandins are key modulators of blood pressure and arterial tone. Prostaglandin E 2 (PGE 2 ), is a prostanoid that has vasodepressor effects; however, under certain circumstances PGE 2 can induce vasopressor responses. Recent reports demonstrated that sub-threshold concentrations of vasoconstrictors augment PGE 2 -mediated constriction in rat femoral arteries. However, whether angiotensin II (Ang II) could affect PGE 2 -mediated contraction is not known. Using a wire myograph, we demonstrated that PGE 2 had no significant effect on mouse femoral arterial rings at doses up to 1 μM. However, priming of arterial rings with 1 nM Ang II potentiated PGE 2 -evoked constriction in a concentration dependent manner (Area Under the Curve, AUC untreated 1.784 ± 0.353, AUC Ang II 23.27± 9.820, P<0.05). We tested femoral arteries from EP1, EP2, and EP3 receptor knockout mice. Only the EP3-/- arteries were unable to respond to PGE 2 after Ang II priming (figure below). Pretreatment of arterial rings with 1 μM losartan, an angiotensin receptor antagonist, blocked PGE 2 -induced constrictor effects primed with Ang II (% of KCl, Ang II 21.72 ± 5.296, Ang II + losartan 3.025 ± 1.046, n=3). We have determined that re-addition of extracellular Ca 2+ to a Ca 2+ -free artery restores PGE 2 -induced contractions (n=5) and that the Rho-kinase inhibitor Y-27632 blocks contraction (n=3). Taken together these data are consistent with angiotensin AT1 and prostaglandin EP3 receptors mediating a synergistic Rho-kinase-dependent contractile response. We are continuing to investigate the relationship between Ang II and PGE 2 to determine the physiological relevance this may have in modulating blood pressure.

scholarly journals Antihypertensive therapy increases tetrahydrobiopterin levels and NO/cGMP signaling in small arteries of angiotensin II-infused hypertensive rats

2011 ◽  
Vol 300 (3) ◽  
pp. H718-H724 ◽  
Author(s):  
Kyu-Tae Kang ◽  
Jennifer C. Sullivan ◽  
Frank T. Spradley ◽  
Livius V. d'Uscio ◽  
Zvonimir S. Katusic ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Triple Therapy ◽  
Antihypertensive Therapy ◽  
Mesenteric Arteries ◽  
Gtp Cyclohydrolase I ◽  
Hypertensive Rats ◽  
Small Arteries ◽  
Enos Phosphorylation ◽  
Cgmp Signaling

We previously reported that small mesenteric arteries from hypertensive rats have increased NOS-derived H2O2 and reduced NO/cGMP signaling. We hypothesized that antihypertensive therapy lowers blood pressure through a tetrahydrobiopterin (BH4)-dependent mechanism restoring NO/cGMP signaling and endothelial NOS (NOS3; eNOS) phosphorylation in small arteries. To test this hypothesis, small mesenteric arteries from normotensive rats (NORM), angiotensin II-infused rats (ANG), ANG rats with triple therapy (reserperine, hydrochlorothiazide, and hydralazine), or ANG rats with oral BH4 therapy were studied. Both triple therapy and oral BH4 therapy attenuated the rise in systolic blood pressure in ANG rats and restored NO/cGMP signaling in small arteries similarly. Triple therapy significantly increased vascular BH4 levels and BH4-to-BH2 ratio similar to ANG rats with BH4 supplementation. Furthermore, triple therapy (but not oral BH4 therapy) significantly increased GTP cyclohydrolase I (GTPCH I) activity in small arteries without a change in expression. NOS3 phosphorylation at Ser1177 was reduced in small arteries from ANG compared with NORM, while NOS3 phosphorylation at Ser633 and Thr495 were similar in ANG and NORM. NOS3 phosphorylation at Ser1177 was restored with triple therapy or oral BH4 in ANG rats. In conclusion, antihypertensive therapy regulates NO/cGMP signaling in small arteries through increasing BH4 levels and NOS3 phosphorylation at Ser1177.

scholarly journals Renal injury in angiotensin II+l-NAME-induced hypertensive rats is independent of elevated blood pressure

2011 ◽  
Vol 300 (4) ◽  
pp. F1008-F1016 ◽  
Author(s):  
Aaron J. Polichnowski ◽  
Limin Lu ◽  
Allen W. Cowley
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Renal Injury ◽  
Interstitial Fibrosis ◽  
Left Kidney ◽  
Fold Increase ◽  
Experimental Hypertension ◽  
Human Populations ◽  
Ang Ii ◽  
Sprague Dawley

The balance between angiotensin II (ANG II) and nitric oxide plays an important role in renal function and is thought to contribute to the progression of renal injury in experimental hypertension. In the present study, we investigated the extent of blood pressure (BP)-dependent and BP-independent pathways of renal injury following 2 wk of hypertension produced by intravenous infusion of ANG II (5 ng·kg−1·min−1)+ Nω-nitro-l-arginine methyl ester (l-NAME; 1.4 μg·kg−1·min−1) in male Sprague-Dawley rats. An aortic balloon occluder was positioned between the renal arteries to maintain (24 h/day) BP to the left kidney (servo-controlled) at baseline levels, whereas the right kidney (uncontrolled) was chronically exposed to elevated BP. Over the 14-day experimental protocol, the average BP to uncontrolled kidneys (152.7 ± 1.8 mmHg) was significantly elevated compared with servo-controlled (113.0 ± 0.2 mmHg) kidneys and kidneys from sham rats (108.3 ± 0.1 mmHg). ANG II+l-NAME infusion led to renal injury that was focal in nature and mainly confined to the outer medulla. Despite the differences in BP between servo-controlled and uncontrolled kidneys, there was a similar ∼3.5-fold increase in renal outer medullary tubular injury, ∼2-fold increase in outer medullary interstitial fibrosis, ∼2-fold increase in outer medullary macrophage infiltration, and a significant increase in renal oxidative stress, all of which are indicative of BP-independent mediated pathways. The results of this study have important implications regarding the pathogenesis of renal injury in various experimental models of hypertension and provide novel insights regarding the variable association observed between hypertension and renal injury in some human populations.

scholarly journals Blood pressure-related attenuation of Angiotensin II-induced contraction in the thoracic aorta from SHRSP at developmental ages of hypertension

1996 ◽  
Vol 37 (4) ◽  
pp. 541-541
Author(s):  
Hideya Mizuno ◽  
Satoshi Mashiko ◽  
Takeshi Onda ◽  
Isao Tomita ◽  
Masahiko Ikeda ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Thoracic Aorta

Renal and vascular effects of chronic nitric oxide synthase inhibition: involvement of endothelin 1 and angiotensin II

1999 ◽  
Vol 77 (1) ◽  
pp. 8-16 ◽  
Author(s):  
Martin D'Amours ◽  
Marcel Lebel ◽  
John H Grose ◽  
Richard Larivière
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Angiotensin Ii ◽  
Systolic Blood Pressure ◽  
Renal Dysfunction ◽  
Thoracic Aorta ◽  
Vascular Effects ◽  
Endothelin 1 ◽  
Mesenteric Arterial Bed

Endothelin 1 (ET-1) is a potent vasoconstrictor implicated in the control of blood pressure and renal function. Its effects can be modulated by nitric oxide (NO), which inhibits ET-1 production and action. Recently, we reported that ET-1 production can also be modulated by angiotensin II (AngII) in vivo. To investigate the interactions between NO, ET-1, and AngII in hypertension and renal dysfunction, we assessed immunoreactive ET-1 (ir-ET-1) concentration in plasma and urine as well as in vascular and renal tissues of rats with chronic inhibition of NO synthesis, in the presence and the absence of the AngII type 1 receptor antagonist losartan. Normal (protocols A and B) and uninephrectomized rats (protocol C) received the L-arginine analog NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, 0.05% (protocol A) or 0.1% (protocols B and C), with or without losartan (20 mg·kg-1·day-1). After 6 weeks, systolic blood pressure was significantly increased in L-NAME rats compared with the controls (p < 0.01), while serum creatinine and urea, creatinine clearance, and proteinuria were similar to control values. However, ir-ET-1 concentration in plasma and in the thoracic aorta was augmented in animals receiving 0.1% L-NAME (p < 0.01), while it was unchanged in the mesenteric arterial bed, preglomerular arteries, and glomeruli. In contrast, ir-ET-1 concentration was decreased in the renal papilla (p < 0.05) as well as in the urine of L-NAME rats (p < 0.01). Treatment with losartan significantly attenuated the rise in systolic blood pressure induced by L-NAME (p < 0.01). Losartan also normalized the increased ir-ET-1 concentration in plasma and in the thoracic aorta, but had no effect on tissues with normal or reduced ir-ET-1 levels. These results indicate that chronic inhibition of NO synthase with L-NAME induces hypertension without renal dysfunction. Increased ET-1 production in some blood vessels and elevated circulating ET-1 concentration may contribute to the maintenance of high blood pressure. The reduction of systolic blood pressure by losartan supports a role for AngII in the pathogenesis of this form of hypertension, which may be due, at least in part, to the modulation of ET-1 production.Key words: endothelin, nitric oxide, L-NAME, angiotensin II, losartan, hypertension, blood vessel, glomeruli.

Abstract P132: A Kidney-Targeted Nanoparticle To Augment Renal Lymphatic Density Decreases Blood Pressure In Mice With L-NAME- And Angiotensin II-Induced Hypertension

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Bethany L Goodlett ◽  
Eunsoo Yoo ◽  
Chang Sun Kang ◽  
Dakshnapriya Balasubbramanian ◽  
Sydney Love ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Immune Cells ◽  
Flow Cytometric Analysis ◽  
Lymphatic Vessels ◽  
Fold Increase ◽  
Lower Systolic Blood Pressure ◽  
Induced Hypertension ◽  
Integral Role ◽  
Lymphatic Vasculature

Chronic interstitial inflammation and renal infiltration of activated immune cells play an integral role in hypertension. Lymphatic vessels attenuate inflammation by trafficking activated immune cells and excess fluid from the interstitial space to lymph nodes. Previously, our laboratory demonstrated that genetically inducing renal lymphangiogenesis could treat hypertension in three different mouse models. In an effort to translate these findings into a clinical treatment, we hypothesized that a targeted nanoparticle could deliver the pro-lymphangiogenic factor VEGF-C156S to the kidney, induce lymphangiogenesis, and lower blood pressure in hypertensive mice. A micellar nanoparticle was developed with the capacity to deliver protein to the kidney, as demonstrated through delivery trials. This nanoparticle was loaded with VEGF-C156S and injected into mice with LNAME-induced hypertension (LHTN) or angiotensin II-induced hypertension (AIIHTN) via tail vein every 3 days. Compared to hypertensive mice injected with VEGF-C156S only (no nanoparticle) every 3 days, nanoparticle-treated mice exhibited a significantly lower systolic blood pressure (SBP) after 4 injections (LHTN SBP: 160±5 vs. 120±3 mmHg, p<0.001; AIIHTN SBP: 150±8 vs. 126±6 mmHg, p=0.03). Immunolabeled kidney sections from nanoparticle-treated LHTN mice showed a significant increase in podoplanin+ pixels, corresponding to an increase in lymphatic vessel density (p<0.01). A 5-fold increase in renal gene expression of podoplanin in nanoparticle-treated LHTN mice further supported this finding (p=0.01). Flow cytometric analysis of the nanoparticle-treated LHTN mice showed decreased renal CD45+F4/80+CD11c- cells, while AIIHTN mice revealed decreased levels of renal CD45+CD3e+, CD45+CD4+CD8-, and CD45+F4/80+CD11c+ cells (p<0.01, p=0.03, and p<0.001, respectively) when compared to their respective hypertensive groups. These data support our previous findings that expanding the renal lymphatic vasculature can treat existing hypertension by reducing renal immune cells. The results of this study may provide clinicians with a renal lymphatic-targeted therapeutic for treating hypertensive patients.

THE FALL OF BLOOD PRESSURE FOLLOWING INDUCTION OF DECIDUOMATA IN STEROID HYPERTENSIVE RATS RECEIVING PROGESTERONE

1968 ◽  
Vol 59 (2) ◽  
pp. 227-234 ◽  
Author(s):  
H. C. Moore ◽  
I. Cserhati ◽  
F. P. Biliczki
Keyword(s):  
Blood Pressure ◽  
Hypotensive Effect ◽  
Hypertensive Rats ◽  
Pregnant Rats ◽  
Hypertensive Rat ◽  
Equivalent Time ◽  
Metrial Gland ◽  
Blood Pressure Responses ◽  
A Minor ◽  
Maternal Decidua

ABSTRACT Experimental deciduomata and progesterone together lower the blood pressure in the steroid hypertensive rat from the 5th to 10th day of decidual growth i. e. from the 10th to 15th day of pseudopregnancy. This would suggest that the fall of blood pressure at an equivalent time of gestation in hypertensive pregnant rats could be due to the maternal decidua under the influence of progesterone. It is further considered that the metrial gland of the deciduoma is more likely to be responsible for the hypotensive effect and by comparison that the metrial gland is implicated in the hypotensive effect of pregnancy. Progesterone alone also exerts a minor hypotensive effect in those animals in which a nephrectomy forms part of the hypertension regimen and indicates one way in which a maternal renal factor could influence blood pressure responses in hypertensive pregnant rats.

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