Does nitric oxide synthesis really contribute to systemic blood pressure control?

1995 ◽  
Vol 13 (6) ◽  
pp. 710 ◽  
Author(s):  
William C. Haynes ◽  
David J. Webb
1995 ◽  
Vol 13 (6) ◽  
pp. 709 ◽  
Author(s):  
Marielle M. E. Krekels ◽  
Frank C. Huvers ◽  
Peter W. de Leeuw ◽  
Nicolaas C. Schaper

1995 ◽  
Vol 13 (10) ◽  
pp. 1221
Author(s):  
Marielle M.E. Krekels ◽  
Frank C. Huvers ◽  
Peter W. de Leeuw ◽  
Nicolaa C. Schaper

Life Sciences ◽  
1995 ◽  
Vol 57 (17) ◽  
pp. 1547-1556 ◽  
Author(s):  
Shyamal Das ◽  
Keshava N. Kumar

1996 ◽  
Vol 135 (4) ◽  
pp. 506-513 ◽  
Author(s):  
Félix Vargas ◽  
Antonio Fernandez-Rivas ◽  
Antonio Osuna

Vargas F, Fernandez-Rivas A, Osuna A. Effects of methimazole in the early and established phases of NG-nitro 4643 c-nitro-l-arginine methyl ester hypertension. Eur J Endocrinol 1996;135:506–13. ISSN 0804– In the present study we evaluated the effects of methimazole, an antithyroid drug, on blood pressure and other variables in the early and established phases of hypertension induced by the inhibition of nitric oxide synthesis with the oral administration of NG-nitro-l-arginine methyl ester (l-NAME), 75 mg/100 ml in the drinking water. Moreover, we also evaluated the acute pressor effect of l-NAME on systemic blood pressure in control and rats treated chronically with methimazole, administered via drinking water (30 mg/100 ml). Oral administration of methimazole maintained the blood pressure of l-NAME-treated rats at normal levels 25 days after induction of hypertension. However, after 25 days of methimazole treatment in rats made hypertensive with l-NAME (for 25 days), high blood pressure was similar in methimazole-treated and non-treated l-NAME rats, despite the fact that a hypothyroid state had been achieved in the methimazole-treated rats. Acute intravenous injection of l-NAME caused a similar increase in mean arterial pressure in control and methimazole-treated rats at the lowest dose; however, smaller pressor responses were observed with increasing doses in hypothyroid rats. These results clearly demonstrate that hypothyroidism induced by methimazole prevents, but does not reverse, l-NAME hypertension and reduces the acute pressor responsiveness to l-NAME administration. F Vargas, Departamento de Fisiología, Facultad de Medicina, E-18012, Granada, Spain


2013 ◽  
Vol 5 (2) ◽  
pp. 60 ◽  
Author(s):  
Mehdi Nematbakhsh ◽  
Fatemeh Eshraghi ◽  
Zahra Pezeshki ◽  
Behzad Zolfaghari ◽  
Tahereh Safari ◽  
...  

Hypertension ◽  
2020 ◽  
Vol 76 (6) ◽  
pp. 1753-1761
Author(s):  
Carmine Savoia ◽  
Emanuele Arrabito ◽  
Rosa Parente ◽  
Carmine Nicoletti ◽  
Luca Madaro ◽  
...  

Angiotensin (1–7) production increases during AT1R (angiotensin type-1 receptor) blockade. The contribution of Ang (1–7) (angiotensin [1–7]) and its receptor (MasR) to the favorable effect of angiotensin receptor blockers on remodeling and function of resistance arteries remains unclear. We sought to determine whether MasR contributes to the improvement of vascular structure and function during chronic AT1R blockade. Spontaneously hypertensive rats were treated with Ang (1–7) or olmesartan ± MasR antagonist A-779, or vehicle, for 14 days. Blood pressure was measured by tail cuff methodology. Mesenteric arteries were dissected and mounted on a pressurized micromyograph to evaluate media-to-lumen ratio (M/L) and endothelial function. Expression of MasR and eNOS (endothelial nitric oxide synthase) was evaluated by immunoblotting, plasma nitrate by colorimetric assay, and reactive oxygen species production by dihydroethidium staining. Independently of blood pressure, olmesartan significantly reduced M/L and improved NO bioavailability, A-779 prevented these effects. Likewise, Ang (1–7) significantly reduced M/L and NO bioavailability. MasR expression was significantly increased by Ang (1–7) as well as by olmesartan, and it was blunted in the presence of A-779. Both Ang (1–7) and olmesartan increased eNOS expression and plasma nitrite which were reduced by A-779. Superoxide generation was attenuated by olmesartan and Ang (1–7) and was blunted in the presence of A-779. These MasR-mediated actions were independent of AT2R activation since olmesartan and Ang (1–7) increased MasR expression and reduced M/L in Ang II (angiotensin II)–infused AT2R knockout mice, independently of blood pressure control. A-779 prevented these effects. Hence, MasR activation may contribute to the favorable effects of AT1R antagonism on NO bioavailability and microvascular remodeling, independently of AT2R activation and blood pressure control.


2003 ◽  
Vol 284 (2) ◽  
pp. F274-F281 ◽  
Author(s):  
Rajash K. Handa ◽  
Jack W. Strandhoy ◽  
Carlos E. Giammattei ◽  
Shelly E. Handa

We examined the hemodynamic and tubular transport mechanisms by which platelet-activating factor (PAF) regulates salt and water excretion. In anesthetized, renally denervated male Wistar rats, with raised systemic blood pressure and renal arterial blood pressure maintained at normal levels, intrarenal PAF infusion at 2.5 ng · min−1 · kg−1resulted in a small fall in systemic blood pressure (no change in renal arterial blood pressure) and an increase in renal blood flow and urinary water, sodium, and potassium excretion rates. The PAF-induced changes in cardiovascular and renal hemodynamic function were abolished and renal excretory function greatly attenuated by treating rats with a nitric oxide synthase inhibitor. To determine whether a tubular site of action was involved in the natriuretic effect of PAF, cortical proximal tubules were enzymatically dissociated from male Wistar rat kidneys, and oxygen consumption rates (Qo 2) were used as an integrated index of transcellular sodium transport. PAF at 1 nM maximally inhibited Qo 2 in both untreated and nystatin-stimulated (sodium entry into renal cell is not rate limiting) proximal tubules by ∼20%. Blockade of PAF receptors or Na+-K+-ATPase pump activity with BN-52021 or ouabain, respectively, abolished the effect of PAF on nystatin-stimulated proximal tubule Qo 2. Inhibition of nitric oxide synthase or guanylate cyclase systems did not alter PAF-mediated inhibition of nystatin-stimulated proximal tubule Qo 2, whereas phospholipase A2 or cytochrome- P-450 monooxygenase inhibition resulted in a 40–60% reduction. These findings suggest that stimulation of PAF receptors on the proximal tubule decreases transcellular sodium transport by activating phospholipase A2 and the cytochrome- P-450 monooxygenase pathways that lead to the inhibition of an ouabain-sensitive component of the basolateral Na+-K+-ATPase pump. Thus PAF can activate both an arachidonate pathway-mediated suppression of proximal tubule sodium transport and a nitric oxide pathway-mediated dilatory action on renal hemodynamics that likely contributes to the natriuresis and diuresis observed in vivo.


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