Effects of methimazole in the early and established phases of NG-nitro-l-arginine methyl ester hypertension

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

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

1986 ◽  
Vol 61 (1) ◽  
pp. 185-191 ◽  
Author(s):  
C. A. Hales ◽  
R. D. Brandstetter ◽  
C. F. Neely ◽  
M. B. Peterson ◽  
D. Kong ◽  
...  

Acute pulmonary and systemic vasomotor changes induced by endotoxin in dogs have been related, at least in part, to the production of eicosanoids such as the vasoconstrictor thromboxane and the vasodilator prostacyclin. Steroids in high doses, in vitro, inhibit activation of phospholipase A2 and prevent fatty acid release from cell membranes to enter the arachidonic acid cascade. We, therefore, administered methylprednisolone (40 mg/kg) to dogs to see if eicosanoid production and the ensuing vasomotor changes could be prevented after administration of 150 micrograms/kg of endotoxin. The stable metabolites of thromboxane B2 (TxB2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) were measured by radioimmunoassay. Methylprednisolone by itself did not alter circulating eicosanoids but when given 2.5 h before endotoxin not only failed to inhibit endotoxin-induced eicosanoid production but actually resulted in higher circulating levels of 6-keto-PGF1 alpha (P less than 0.05) compared with animals receiving endotoxin alone. Indomethacin prevented the steroid-enhanced concentrations of 6-keto-PGF1 alpha after endotoxin and prevented the greater fall (P less than 0.05) in systemic blood pressure and systemic vascular resistance with steroid plus endotoxin than occurred with endotoxin alone. Administration of methylprednisolone immediately before endotoxin resulted in enhanced levels (P less than 0.05) of both TxB2 and 6-keto-PGF1 alpha but with a fall in systemic blood pressure and vascular resistance similar to the animals pretreated by 2.5 h. In contrast to the early steroid group in which all of the hypotensive effect was due to eicosanoids, in the latter group steroids had an additional nonspecific effect. Thus, in vivo, high-dose steroids did not prevent endotoxin-induced increases in eicosanoids but actually increased circulating levels of TxB2 and 6-keto-PGF1 alpha with a physiological effect favoring vasodilation.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K.A Dumont ◽  
R Persson ◽  
J.P Kvitting ◽  
R Lundblad ◽  
R Haaverstad ◽  
...  

Abstract Background Barlow's disease provides both diagnostic and therapeutic challenges. The impact of systemic blood-pressure on severity of regurgitation is still unclear. Purpose We hypothesized that mitral annulus behaves passively with enlargement during ventricular systole, and secondly, we tested the hypothesis that severity of regurgitation correlates to systemic blood-pressure (BP) of the patient. Methods Ten patients with Barlow's disease were compared with 10 healthy controls. Brachial blood-pressure was measured according to guidelines. Transthoracic 3D echo was obtained from an apical view (38.6±8.2 frames per second). Data was analyzed using a holographic display. We measured commissure width (CW), septallateral length (SL) and mitral annular surface area throughout the cardiac cycle. Aortic flow ejection time was derived from continuous Doppler across the aortic valve. Timing of aortic valve closure was visually assessed by 3D echo. Onset and end of mitral regurgitation was derived from continuous wave Doppler of transmitral flow. Results Systolic BP in controls and patients were 122±5 and 133±12 mmHg, respectively (p<0.05). Enddiastolic volume was 87±7 ml/m2 (controls) and 100±14 ml/m2 (Barlow), p<0.02. Left ventricular EF in controls and patients were 59±5 and 62±5%, respectively, p=NS. Barlow patients had moderate or severe late systolic regurgitation with mean regurgitation volume of 51±18 ml. Annular surface area, CW and SL behaved passively with enlargement during ventricular systole (Figure 1). Peak systolic surface area, CW and SL in healthy controls and Barlow patients were 8.7±0.5 vs 20.7±3.2 cm2 (p<0.001), 30.1±1.5 vs 49.5±4.9 mm (p<0.001) and 30.9±1.5 vs 44.9±3.3 mm (p<0.001). Peak annular surface area and regurgitation volume in patients showed a positive correlation with systolic BP (y = 0.156x − 0.077, r=0.60 and y = 1.136x − 99.7, r=0.80, respectively). Conclusions We have demonstrated pressure constrained mitral annular dysfunction in Barlow's disease, indicating that systemic blood pressure may modify the severity of regurgitation. The study provides novel insights into mechanisms of mitral regurgitation and potential therapeutic actions in the future. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Grieg Foundation


2016 ◽  
Vol 34 (Supplement 1) ◽  
pp. e121
Author(s):  
Fernando Garcia ◽  
Beatriz Fidale ◽  
Sebastião Ferreira-Filho

2012 ◽  
Vol 110 (3) ◽  
pp. 378-382 ◽  
Author(s):  
Jari Antero Laukkanen ◽  
J. Richard Jennings ◽  
Jussi Kauhanen ◽  
Timo Heikki Mäkikallio ◽  
Kimmo Ronkainen ◽  
...  

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