Thromboxane A2-prostaglandin H2 and renovascular hypertension in rats

1994 ◽  
Vol 267 (5) ◽  
pp. R1190-R1197 ◽  
Author(s):  
E. H. Boussairi ◽  
J. Sacquet ◽  
J. Sassard ◽  
D. Benzoni

To evaluate the contribution of thromboxane (Tx) A2-prostaglandin (PG) H2 in two-kidney, one-clip Goldblatt hypertension (GH), 26 GH rats were chronically treated (GHT) with a specific TxA2-PGH2 receptor antagonist, CGS-22652 (30 mg.kg-1.24 h-1 sc); 28 others as well as 17 sham-clipped (SC) rats received vehicle. Twelve GH and 3 GHT rats developed malignant hypertension and died. After 6 wk of treatment, GH rats exhibited higher mean blood pressure (BP; 189 +/- 3 vs. 118 +/- 2 mmHg) and an increased vascular reactivity to the main pressor agents compared with SC rats. Chronic TxA2-PGH2 receptor blockade lowered mean BP in 13 GHT rats (125 +/- 3 mmHg) and decreased their vascular reactivity compared with GH rats. However, 10 GHT rats remained hypertensive (190 +/- 9 mmHg) and differed from the former by an increased vascular reactivity to vasopressin. It is concluded that renal artery clipping induces either benign or malignant hypertension. In benign forms, TxA2-PGH2 blockade normalizes BP through decreasing the vascular responsiveness to the main pressor agents. In malignant forms, it limits the elevation of BP and markedly reduces mortality.

1976 ◽  
Vol 54 (3) ◽  
pp. 314-321
Author(s):  
A. C. Darke ◽  
P. G. Nair ◽  
P. Gaskell

The possible role of increased vascular reactivity in the mechanism of experimental hypertension was studied by measurements of the critical opening pressure (COP) of tail vessels in conscious rats. In hypertension induced by administration of desoxycorticosterone acetate (DOCA) and replacement of the drinking water by 1% NaCl solution (DOCA–NaCl hypertension), and in one-kidney Goldblatt renovascular hypertension, the raised level of blood pressure was associated with an increased COP of the tail vessels when measured both before and after ganglionic blockade. In rats treated with either DOCA alone or 1% NaCl alone there was no significant increase in systolic blood pressure (SBP) or COP relative to the corresponding controls. In all four experimental series intravenous infusion of angiotensin or norepinephrine in conscious ganglion-blocked rats produced dose-dependent increases in SBP and COP. In DOCA–NaCl hypertensive rats but not in renovascular hypertensives, nor in rats treated with DOCA alone or 1% NaCl alone, the increase in COP for a given increment in dose of angiotensin or norepinephrine was significantly greater than in the control rats. It is concluded that in DOCA–NaCl hypertension there is a true increase in the reactivity of the smooth muscle of the resistance vessels to angiotensin and norepinephrine. In renovascular hypertension this is not the case and other factors must therefore be involved in causing the increased blood pressure and COP.


2011 ◽  
Vol 301 (3) ◽  
pp. F615-F621 ◽  
Author(s):  
John N. Lorenz ◽  
Valerie M. Lasko ◽  
Michelle L. Nieman ◽  
Thomas Damhoff ◽  
Vikram Prasad ◽  
...  

Endogenous cardiotonic steroids, through their interaction with the ouabain-binding site of the Na-K-ATPase α-subunit, have been implicated in a variety of cardiovascular disease states including hypertension. We have previously shown that ACTH-induced hypertension is abolished in mutant mice expressing ouabain-resistant α1- and α2-subunits. To further evaluate hypertension resistance in these mutant mice, we examined blood pressure changes in a modified model of 2-kidney, 1-clip (2K1C) renovascular hypertension. To reliably generate 2K1C hypertension, we used polyvinyl tubing (inner diameter: ∼0.27 mm) to accurately gauge the degree of renal artery stenosis. Using this method, virtually all of the clipped mice became hypertensive and there was no incidence of apparent renal ischemia. By telemetry, in response to renal artery clipping, blood pressure in wild-type mice (α1 ouabain-resistant, α2 ouabain-sensitive) increased from 97 ± 3 to 136 ± 7 mmHg. In α1-resistant, α2-resistant mice, pressure increased from 93 ± 2 to 123 ± 4 mmHg, and in α1-sensitive, α2-resistant mice, blood pressure increased from 95 ± 2 to 139 ± 5 mmHg. Blood pressure changes were equivalent in all three groups. In sham mice, blood pressure did not change (96 ± 1 to 95 ± 2 mmHg). Renin mRNA expression was dramatically elevated in the left vs. the right kidney, and plasma renin concentration was elevated similarly in all genotypes. These data indicate that sensitivity of the α1- or α2-Na-K-ATPase binding site to cardiotonic steroids is not a prerequisite for the development of 2K1C renovascular hypertension. In addition, use of a polyurethane cuff to constrict the renal artery provides a reliable method for producing 2K1C hypertension in mice.


2017 ◽  
Vol 126 (2) ◽  
pp. 321-324
Author(s):  
Edward D. Miller

Abstract Inhibition of Angiotensin Conversion in Experimental Renovascular Hypertension. By Miller ED Jr, Samuels A, Haber E, and Barger AC. Science 1972; 177:1108–9. Reprinted with permission from AAAS. Constriction of the renal artery and controlled reduction of renal perfusion pressure is followed by a prompt increase in systemic renin activity and a concomitant rise in blood pressure in trained, unanesthetized dogs. The elevated blood pressure induced by the renal artery stenosis can be prevented by prior treatment with the nonapeptide Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro, which blocks conversion of angiotensin I to angiotensin II. Further, the nonapeptide can restore systemic pressure to normal in the early phase of renovascular hypertension. These results offer strong evidence that the renin– angiotensin system is responsible for the initiation of hypertension in the unilaterally nephrectomized dog with renal artery constriction.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Takuya Higashitani ◽  
Daisuke Aono ◽  
Mitsuhiro Kometani ◽  
Shigehiro Karashima ◽  
Masashi Demura ◽  
...  

Abstract Renovascular hypertension (RVHT) is an important and potentially treatable form of resistant hypertension. Hypercortisolemia could also cause hypertension and diabetes mellitus. We experienced a case wherein adrenalectomy markedly improved blood pressure and plasma glucose levels in a patient with RVHT and subclinical Cushing’s syndrome. A 62-year-old Japanese man had been treated for hypertension and diabetes mellitus for 10 years. He was hospitalized because of disturbance in consciousness. His blood pressure (BP) was 236/118 mmHg; pulse rate, 132 beats/min; and plasma glucose level, 712 mg/dl. Abdominal computed tomography scanning revealed the presence of bilateral adrenal masses and left atrophic kidney. Abdominal magnetic resonance angiography demonstrated marked stenosis of the left main renal artery. The patient was subsequently diagnosed with atherosclerotic RVHT with left renal artery stenosis. Bilateral adrenal masses were immunohistologically identified as potential sites for cortisol overproduction. Therefore, laparoscopic left nephrectomy and adrenalectomy were simultaneously performed resulting in improved BP and glucose levels. Pathological studies revealed the presence of multiple cortisol-producing adrenal nodules and aldosterone-producing cell clusters in the adjacent left adrenal cortex. In the present case, activated renin-angiotensin-aldosterone system and cortisol overproduction resulted in severe hypertension, which was managed with simultaneous unilateral nephrectomy and adrenalectomy.


2021 ◽  
Author(s):  
Michelle Sabino de Souza Nunes Faria ◽  
Vinicius Eduardo Pimentel ◽  
Julia Venturini Helaehil ◽  
Mayara Correa Bertolo ◽  
Nathalia Tonus Horas Santos ◽  
...  

Background: Caloric restriction (CR) is a type of dietary intervention enjoyed as an essential tool in weight loss by modulating critical pathways of metabolic control, although it is not yet clear what repercussions this intervention model results when associated with renovascular hypertension. Here we demonstrate that CR can be beneficial in obese and hypertensive animals. Methods: Rats were divided into groups: SHAM, and two groups underwent surgery to clip the left renal artery, to induce renovascular hypertension (OH and OHR). The SHAM diet was performed: 14 weeks normolipidic diet; OH: 2 weeks normolipidic diet + 12 weeks hyperlipidic diet, both ad libitum; OHR: 2 weeks normolipidic diet + 8 weeks ad libitum high fat diet + 4 weeks restricted 40% high fat diet. Results: the OHR group dissipated blood pressure, body weight and glucose homeostasis. Reductions in insulinemia, lipids, islets fibrotic areas in the OHR group were observed along with increased insulin sensitivity and normalization of the insulin-degrading enzyme. Nicotinamide phosphoribosyltransferase, insulin receptor, Sirtuin 1 and complex II protein were modulated in liver tissue in the OHR group. Strong correlations, direct or indirect, were evaluated by Spearmans model between SIRT1, AMPK, NAMPT, PGC-[alpha]; and NNMT with the reestablishment of blood pressure, weight loss, glycidic and lipid panel and mitochondrial adaptation. Conclusion: CR provided short-term beneficial effects to recover physiological parameters induced by a high-fat diet and renal artery stenosis in obese and hypertensive animals. These benefits, even in the short term, can bring physiological benefits in the long run.


2014 ◽  
Vol 117 (12) ◽  
pp. 1417-1423 ◽  
Author(s):  
Jody L. Greaney ◽  
Anna E. Stanhewicz ◽  
W. Larry Kenney ◽  
Lacy M. Alexander

The cutaneous circulation is used to examine vascular adrenergic function in clinical populations; however, limited studies have examined whether there are regional limb and sex differences in microvascular adrenergic responsiveness. We hypothesized that cutaneous adrenergic responsiveness would be greater in the leg compared with the arm and that these regional limb differences would be blunted in young women ( protocol 1). We further hypothesized that cutaneous vasoconstriction to exogenous norepinephrine (NE) during β-adrenergic receptor antagonism would be augmented in young women ( protocol 2). In protocol 1, one microdialysis fiber was placed in the skin of the calf and the ventral forearm in 20 healthy young adults (11 men and 9 women). Laser-Doppler flowmetry was used to measure red blood cell flux in response to graded intradermal microdialysis infusions of NE (10−12 to 10−2 M). In protocol 2, three microdialysis fibers were placed in the forearm (6 men and 8 women) for the local perfusion of lactated Ringer (control), 5 mM yohimbine (α-adrenergic receptor antagonist), or 2 mM propranolol (β-adrenergic receptor antagonist) during concurrent infusions of NE (10−12 to 10−2 M). There were no limb or sex differences in cutaneous adrenergic responsiveness (logEC50) to exogenous NE. During α-adrenergic receptor blockade, women had greater exogenous NE-induced cutaneous vasodilation at the lowest doses of NE (10−12 to 10−10 M). Collectively, these data indicate that there are no limb or sex differences in cutaneous adrenergic responsiveness to exogenous NE; however, young women have a greater β-adrenergic receptor-mediated component of the vascular responsiveness to exogenous NE.


1975 ◽  
Vol 228 (5) ◽  
pp. 1415-1422 ◽  
Author(s):  
G Constantopoulos ◽  
M Kusumoto ◽  
JM Rojo-Ortega ◽  
P Granger ◽  
R Boucher ◽  
...  

In dogs made hypertensive renal artery stenosis and contralateral nephrectomy, the arterial and myocardial tissue content of water, cations (sodium, potassium, magnesium, calcium), and norepinephrine was measured 20 and 60 days after the operation. Hypertensive animals autopsied at the earlier stage of hypertension had significantly lower (-25 to-50%, P smaller than 0.01) arterial norepinephrine than either the sham or nonhypertensive animals. The water and cation content of arteries was unchanged, but aortic tissue contained significantly more water, sodium, potassium, and magnesium than the nonhypertensives. Hypertensives autopsied at 60 days also had lower arterial norepinephrine content than sham and nonhypertensive animals, but this refuction was not significant. Their arterial and aortic tissue contained more water and cations than the nonhypertensive, sham, unoperated, and unilaterally nephrectomized dogs. It is suggested that in the initial stage of renovascular hypertension the arterial norepinephrine content is reduced significantly, whereas at a later stage the arterial water and cations may be involved in the maintenance of an elevated blood pressure.


1973 ◽  
Vol 45 (s1) ◽  
pp. 309s-310s ◽  
Author(s):  
H. M. Pinedo ◽  
J. De Graeff ◽  
A. Struyvenberg

1. A comparison has been made of surgical and medical treatment in patients with arteriosclerotic renal artery stenosis and hypertension. 2. Immediate post-operative blood pressure was often normal, but frequently rose again later. After the sixth year only about 25% of surgical patients were normotensive without drug treatment. 3. Nephrectomy and vascular reconstruction gave similar results. 4. We presently believe that post-operative anticoagulant therapy is indicated in patients undergoing surgery for arteriosclerotic renal artery stenosis.


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