Antihypertensive actions of angiotensin-(1-7) in spontaneously hypertensive rats

1995 ◽  
Vol 269 (1) ◽  
pp. H313-H319 ◽  
Author(s):  
I. F. Benter ◽  
C. M. Ferrario ◽  
M. Morris ◽  
D. I. Diz
Keyword(s):  
Blood Pressure ◽  
Prostaglandin E2 ◽  
Spontaneously Hypertensive Rats ◽  
Systolic Pressure ◽  
Experimental Hypertension ◽  
Electrolyte Balance ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Plasma Vasopressin

Observations that angiotensin-(1-7) [ANG-(1-7)] may oppose the vasoconstrictor actions of angiotensin II (ANG II) prompted an investigation of the effects of the heptapeptide on the maintenance of elevated blood pressure in spontaneously hypertensive rats (SHR). ANG-(1-7) (24 micrograms.kg-1.h-1) was infused into the jugular vein of 13-wk-old SHR (n = 64), Wistar-Kyoto (WKY, n = 50), and Sprague-Dawley (SD, n = 18) rats for 2 wk, with the use of osmotic minipumps. Blood pressure, fluid and electrolyte balance, plasma vasopressin, and urinary excretion of prostaglandin E2 and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) were measured at days 2, 7, and 12 of the infusion. In SHR, ANG-(1-7) caused a sustained and significant reduction in plasma vasopressin concentration that was associated with an increase in urinary prostaglandin E2 and 6-keto-PGF1 alpha excretion at day 2 after the commencement of the infusion. These changes were accompanied by diuresis and natriuresis during the first 3 days of infusion in SHR but not in WKY or SD rats. Direct measurements of arterial pressure confirmed the lowering effect of ANG-(1-7) on systolic pressure of SHR on day 2 of treatment with a restoration of the pressure by days 7 and 12. These findings, along with our previous demonstration that ANG-(1-7) is an active depressor peptide in the intact animal, suggest that ANG-(1-7) may play a significant role as a vasodepressor system opposing the hemodynamic actions of ANG II in this genetic form of experimental hypertension.

Gonadectomy-induced reduction of blood pressure in adult spontaneously hypertensive rats

1982 ◽  
Vol 101 (1) ◽  
pp. 154-160 ◽  
Author(s):  
Yoshiko Masubuchi ◽  
Toshio Kumai ◽  
Akiyo Uematsu ◽  
Kenji Komoriyama ◽  
Masanao Hirai
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Adrenal Glands ◽  
Systolic Pressure ◽  
Pressure Rise ◽  
Progressive Increase ◽  
Hormonal Changes ◽  
Hypertensive Rats ◽  
Male And Female ◽  
Spontaneously Hypertensive

Abstract. Adult male and female spontaneously hypertensive rats (SHR-Okamoto, Kyoto) were gonadectomized when they were 17 weeks old. Intact SHR showed a progressive increase of their blood pressure with growth, attaining systolic pressure levels of 194–208 in males and 163–173 mmHg in females when they were 29–30 weeks old. During this same period, the gonadectomized animals showed a significant reduction in blood pressure ranging from 168–175 in males and from 158–163 mmHg in females. These studies indicate that male and female SHR gonadectomized at 17 weeks of age do not show the progressive blood pressure rise that occurs in intact SHR. There was no change in heart rate in either sex. Corticosterone (B) levels in plasma were increased in the orchidectomized males, and 18-OH-DOC levels in plasma were increased in the adrenal glands of ovariectomized females indicating that these hormonal changes probably do not play a role in SHR hypertension. It appears that gonadal and other hormones are involved in the pathogenesis of SHR hypertension.

scholarly journals Reconstitution of autophagy ameliorates vascular function and arterial stiffening in spontaneously hypertensive rats

2019 ◽  
Vol 317 (5) ◽  
pp. H1013-H1027 ◽  
Author(s):  
Cameron G. McCarthy ◽  
Camilla F. Wenceslau ◽  
Fabiano B. Calmasini ◽  
Nicole S. Klee ◽  
Michael W. Brands ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vascular Function ◽  
Spontaneously Hypertensive Rats ◽  
Cellular Aging ◽  
Experimental Hypertension ◽  
Dependent Manner ◽  
Vascular Aging ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Autophagic Activity

Insufficient autophagy has been proposed as a mechanism of cellular aging, as this leads to the accumulation of dysfunctional macromolecules and organelles. Premature vascular aging occurs in hypertension. In fact, many factors that contribute to the deterioration of vascular function as we age are accelerated in clinical and experimental hypertension. Previously, we have reported decreased autophagy in arteries from spontaneously hypertensive rats (SHRs); however, the effects of restoring autophagic activity on blood pressure and vascular function are currently unknown. We hypothesized that reconstitution of arterial autophagy in SHRs would decrease blood pressure and improve endothelium-dependent relaxation. We treated 14- to 18-wk-old Wistar rats ( n = 7 vehicle and n = 8 trehalose) and SHRs ( n = 7/group) with autophagy activator trehalose (2% in drinking water) for 28 days. Blood pressure was measured by radiotelemetry, and vascular function and structure were measured in isolated mesenteric resistance arteries (MRAs) using wire and pressure myographs, respectively. Treatment with trehalose had no effect on blood pressure in SHRs; however, isolated MRAs presented enhanced relaxation to acetylcholine, in a cyclooxygenase- and reactive oxygen species-dependent manner. Similarly, trehalose treatment shifted the relaxation to the Rho kinase (ROCK) inhibitor Y-27632 to the right, indicating reduced ROCK activity. Finally, trehalose treatment decreased arterial stiffness as indicated by the slope of the stress-strain curve. Overall these data indicate that reconstitution of arterial autophagy in SHRs improves endothelial and vascular smooth muscle function, which could synergize to prevent stiffening. As a result, restoration of autophagic activity could be a novel therapeutic for premature vascular aging in hypertension. NEW & NOTEWORTHY This work supports the concept that diminished arterial autophagy contributes to premature vascular aging in hypertension and that therapeutic reconstitution of autophagic activity can ameliorate this phenotype. As vascular age is a new clinically used index for cardiovascular risk, understanding this mechanism may assist in the development of new drugs to prevent premature vascular aging in hypertension. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/behind-the-bench-episode-one-cam-squared/ .

The Relationship Between Angiotensin II (ANG II) and Oxidative Stress in the Maintenance of Mean Arterial Pressure (MAP) of Spontaneously Hypertensive Rats.

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 686-686
Author(s):  
Rodney J Bolterman ◽  
Clara M Ortiz-Ruiz ◽  
Luis A Juncos ◽  
Jane F Reckelhoff ◽  
Juan C Romero
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Plasma Levels ◽  
Spontaneously Hypertensive Rats ◽  
Enzyme Inhibitor ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Converting Enzyme Inhibitor

48 Spontaneously hypertensive rats (SHR) reportedly have inappropriately high levels of Ang II despite normal plasma renin activity (PRA). Because Ang II stimulates oxidative stress, which in turn quenches nitric oxide, it is possible that Ang II-induced increases in oxidative stress contribute to the increase in blood pressure. Indeed, administering either a converting enzyme inhibitor (to decrease Ang II) or Tempol (a potent antioxidant) reduces blood pressure in SHR. We tested whether decreasing Ang II with a converting enzyme inhibitor reduces oxidative stress as well as MAP in SHR. For this, we divided 12 weeks old SHR into two groups (n=5 each). One group was treated with captopril (100 mg/kg/day added to the drinking water) and the other served as our untreated time controls. After 16 days of treatment, the rats were anesthetised and we measured MAP and collected blood samples to determine PRA, and the plasma levels of Ang II and thiobarbituric acid-reactive substances (TBARS). The captopril-treated rats had a lower MAP than the untreated rats (92±4 vs. 160±5 mmHg, respectively) and an increased PRA (42±1 vs. 26±6 ng/ml/h; captopril-treated vs. untreated rats, respectively). The decreased MAP in the captopril-treated SHR was accompanied by reduced plasma levels of Ang II (630±47 vs. 836±205 pg/ml) and TBARS (5.4±1.0 vs. 3.0±0.2 nmol/ml). Despite the significant decrease in Ang II levels in the captopril-treated SHR, they are still 20-fold higher rhan in normotensive Sprague-Dawley rats (34.0±8.8 pg/ml). In summary, captopril-induced decreases of MAP in SHR are accompanied not only by reduced levels of Ang II, but also by reduced oxidative stress. Because antioxidants also lower MAP in SHR, it suggests that oxidative stress induced by Ang II may play a role in the pathogenesis of the increased blood pressure in SHR.

Altered Cardiac β-adrenoreceptors in Spontaneously Hypertensive Rats Receiving Salt Excess

1980 ◽  
Vol 59 (s6) ◽  
pp. 169s-170s ◽  
Author(s):  
A. A. MacPhee ◽  
H. L. Blakesley ◽  
Karen A. Graci ◽  
E. D. Frohlich ◽  
F. E. Cole
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Tap Water ◽  
Heart Weight ◽  
Experimental Hypertension ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Age Related ◽  
Clinical Hypertension ◽  
Logarithmic Relationship

1. Altered adrenergic responsiveness of hearts and blood vessels occurs in both experimental and clinical hypertension. 2. Since salt excess aggravates both types of hypertension, we investigated β-adrenoreceptor properties in the hearts of spontaneously hypertensive and normotensive rats drinking 1% NaCl or tap water for 3 weeks. 3. Sodium loading increased heart weight in both spontaneously hypertensive and normotensive rats. 4. In spontaneously hypertensive rats excess salt attenuated the age-related decrease in β-adrenoreceptor number observed in spontaneously hypertensive and normotensive rats drinking tap water and in normotensive rats drinking 1% NaCl. 5. Unlike the normotensive rats, which did not show a relationship between β-adrenoreceptor number and blood pressure, spontaneously hypertensive rats on tap water and 1% NaCl showed a significant negative logarithmic relationship between these two variables. These data provide further evidence implicating sodium excess as an aggravating factor in this model of experimental hypertension.

Abstract P241: Autophagic Flux is Diminished in Mesenteric Resistance Arteries of Spontaneously Hypertensive Rats

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Cameron G McCarthy ◽  
Camilla F Wenceslau ◽  
R. Clinton Webb
Keyword(s):  
Blood Pressure ◽  
High Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Cellular Aging ◽  
Experimental Hypertension ◽  
Autophagic Flux ◽  
Vascular Aging ◽  
Resistance Arteries ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Autophagy is the constitutively active catabolic process regulating protein quality control and energy homeostasis. However, dysregulation of this process can have detrimental effects on cellular function. In particular, insufficient autophagy has been proposed as a mechanism of cellular aging, as this leads to the accumulation of damaged macromolecules and organelles. Hypertension is a condition of vascular aging. In fact, many factors that contribute to the deterioration of vascular function as we age are exacerbated in clinical and experimental hypertension. Nonetheless, whether high blood pressure per se is the cause or effect of diminished autophagy remains to be clarified. We hypothesized that mesenteric resistance arteries (MRA) from spontaneously hypertensive rats (SHR) would have decreased autophagic flux as measured by conversion of microtubule-associated protein light chain 3 (LC3-I to LC3-II) compared to normotensive Wistar Kyoto rats (WKY). We observed that MRA from male 12-15 week old SHR have decreased basal expression both cytosolic LC3 (LC3-I) and phosphatidylethanolamine conjugated LC3 (LC3-II), and expression of these proteins are similarly decreased in SHR chronically treated with hydrochlorothiazide and reserpine (SHR+HCTZ/Res) [Arbitrary units (AU), LC3-1: WKY: 1.4±0.1, SHR: 1.1±0.1*, and SHR+HCTZ/Res: 0.7±0.1*; LC3-II: WKY: 1.4±0.1, SHR: 1.1±0.1*, and SHR+HCTZ/Res: 0.7±0.1*, *p<0.05 vs. WKY]. To understand autophagic flux, some MRA were incubated with lysosomal inhibitor chloroquine (CQ; 30 μM) for 2 hours. CQ incubation significantly increased LC3-II expression to a similar magnitude in WKY, SHR, and SHR+HCTZ/Res MRA (all *p<0.05 vs. basal). However, the percent increase in LC3-II expression after CQ incubation was significantly less in SHR compared to WKY, and SHR+HCTZ/Res was not different from either WKY or SHR (% increase from basal LC3-II, WKY: 546±187, SHR: 156±38*, and SHR+HCTZ/Res: 273±106, *p<0.05 vs. WKY). Overall, these data suggest that SHR have impaired autophagosome-lysosomal fusion, and this is not solely attributable to high blood pressure. Therefore, reconstituting autophagic activity could be a novel prophylactic or therapeutic measure against vascular aging in hypertension.

scholarly journals Antihypertensive Activity of Eucommia Ulmoides Oliv: Male Flower Extract in Spontaneously Hypertensive Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Zhen-Jiang Ding ◽  
Chao Liang ◽  
Xiao Wang ◽  
Xin Yao ◽  
Ruo-Han Yang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Aqueous Extract ◽  
Spontaneously Hypertensive Rats ◽  
Male Flower ◽  
Antihypertensive Activity ◽  
Eucommia Ulmoides ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Male Flowers

Eucommia ulmoides Oliv. is a traditional medical plant in Asia; however, it is still unknown whether Eucommia male flowers have an antihypertensive activity. In this study, we found that the aqueous extract of Eucommia ulmoides Oliv. male flowers can lower the blood pressure of SHR in a dose-dependent manner. Mechanistic studies suggested that the aqueous extract of male flowers can promote the mRNA and protein expressions of ACE2 in the kidney of SHR. ELISA assay showed that the plasma levels of ANG II was decreased, while ANG-(1–7) was increased in SHR treated with the aqueous extract of male flowers. ACE2 inhibitor DX600 can reverse the aqueous extract of Eucommia ulmoides Oliv. male flower-induced downregulation of Ang II and upregulation of Ang-(1–7), as well as the reduction of blood pressure in SHR. Moreover, Ang-(1–7)-Mas receptor antagonist A-779 abolished the antihypertensive effects of the aqueous extract of Eucommia ulmoides Oliv. male flower in SHR. The aqueous extract of Eucommia ulmoides Oliv. male flowers exhibited an antihypertensive action through the activation of ACE2-Ang-(1–7)-Mas signaling pathways in spontaneously hypertensive rats.

Expression of smooth muscle MyHC B in blood vessels of hypertrophied heart in experimentally hypertensive rats

2003 ◽  
Vol 284 (2) ◽  
pp. R607-R610 ◽  
Author(s):  
Katharina Wetzel ◽  
Ovidiu Baltatu ◽  
Benno Nafz ◽  
Pontus B. Persson ◽  
Hannelore Haase ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Adaptive Response ◽  
Spontaneously Hypertensive Rats ◽  
Expression Patterns ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Genetic Origin ◽  
Spontaneously Hypertensive ◽  
Muscle Myosin

We demonstrated recently a significantly lower fraction of cardiac precapillary arterioles that expressed smooth muscle myosin heavy chain (MyHC) B (SMB) in spontaneously hypertensive rats. To clarify whether this reduction of SMB expression is of genetic origin, we investigated SMB expression in cardiac precapillary arterioles of normotensive and experimentally hypertensive rats (one clip, one kidney or ANG II minipump). We observed similar SMB expression patterns in precapillary arterioles of experimentally hypertensive rats compared with normotensive controls. These observations suggest that the downregulation of SMB in spontaneously hypertensive rats is of genetic origin rather than an adaptive response to chronically enhanced blood pressure and cardiac hypertrophy.

Antibiotics attenuate experimental hypertension in rats

1985 ◽  
Vol 105 (3) ◽  
pp. 347-350 ◽  
Author(s):  
J. W. Honour ◽  
S. P. Borriello ◽  
U. Ganten ◽  
P. Honour
Keyword(s):  
Blood Pressure ◽  
Oral Administration ◽  
High Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Experimental Hypertension ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Intramuscular Injections ◽  
Sprague Dawley Rats

ABSTRACT Hypertension was produced in Sprague–Dawley rats by intramuscular injections of either corticosterone or ACTH. Lower increases in blood pressure to these challenges were observed in Sprague–Dawley rats pretreated with neomycin or vancomycin which alone had no effect on blood pressure or growth. The development of high blood pressure in spontaneously hypertensive rats of a stroke-prone substrain was also attenuated by oral administration of neomycin. These results suggest that experimental hypertension can be modulated by the administration of antibiotics. J. Endocr. (1985) 105, 347–350

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