Unchanged cardiac angiotensin II levels accompany losartan-sensitive cardiac injury due to nitric oxide synthase inhibition

Verhagen, A. Marjan G.; Hohbach, Jan; Joles, Jaap A.; Braam, Branko; Boer, P. de; Koomans, Hein A.; Gröne, Hermann Josef

doi:10.1016/s0014-2999(00)00384-8

Cited by 14 publications

(6 citation statements)

References 33 publications

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“…In addition, the reninangiotensin system is probably also involved, although similar previous studies have reported both 'involvement' and 'no involvement'. Verhagen et al found that the hemodynamic changes induced by NO inhibition did not affect the renin -angiotensin system, 17 but increases in angiotensin II have also been reported. 18 Hernandez et al found that during NO inhibition, angiotensin II increased vascular resistance.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of Angiotensin-Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker on Atrial Natriuretic Peptide

Sata

Tanaka

Suzuki

et al. 2003

Circ J

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umerous vasoactive substances are involved in the regulation of blood pressure, including reninangiotensin, atrial natriuretic peptide (ANP), endothelium-derived relaxing factor (EDRF), endothelin, and adrenomedullin. In 1986, it was established that EDRF is nitric oxide (NO), 1 which is secreted by vascular endothelial cells and maintains the homeostasis of vascular walls. The main effects of endothelim-derived NO in the circulatory system are relaxation of vascular smooth muscle and regulation of blood pressure. ANP was first isolated and characterized in 1984. 2 It is primarily synthesized and stored as granules in the cardiac atrium, and rapidly released into the blood stream during increased atrium Circulation Journal Vol.67, December 2003 load. The major effects of ANP are lowering of blood pressure, and water and sodium diuresis; and thus it is an important hormone in blood pressure regulation. The renin -angiotensin system also plays an important role in regulating blood pressure. Both angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blocker (ARB) are hypotensive agents that are involved in this system, and these agents are most useful drugs in the clinical setting because they have cardioprotective actions.Previous studies have reported on the administration of NO inhibitors, which increase blood pressure, and have dealt with the administration of ACEI and ARB. However, there is little information on the evaluation of ANP mRNA expression, ANP granules, ANP immunostaining, and changes in plasma ANP concentrations. Therefore, the present study examined the relationship between NO and ANP as vasoactive substances. Methods NO Inhibitor TreatmentNormotensive rats (Jcl: Wistar males, 30-40 g, 3 weeks old) were purchased from CLEA Japan (Kagoshima, Japan). Treatment was started at age 4 weeks and continued for 8 weeks. NO inhibitor was mixed into the food, and The aim of this study was to evaluate the effectiveness of an angiotensin-converting enzyne inhibitor (ACEI, quinapril) or angiotensin II receptor blocker (ARB, candesartan) on atrial natriuretic peptide (ANP) activity in rats with hypertension induced by nitric oxide (NO) inhibition. ACEI and ARB have a number of pharmacologic effects, including blood pressure reduction, myocardial preservation, and an unknown effect in the circulation. The changes in ANP in NO inhibitor-induced hypertensive rats were evaluated in order to elucidate the interaction between ANP and NO in the regulation of blood pressure. Thirty-six rats were divided into 4 groups and administered the experimental agents for 8 weeks: group Control was given regular food (n=9), group N G -nitro-L-arginine (L-NNA) was administered L-NNA (25mg·kg -1 ·day -1 , n=9), group ACEI was administered L-NNA and quinapril (10 mg·kg -1 ·day -1 , n=9), and group ARB was administered L-NNA and candesartan (10mg·kg -1 · day -1 , n=9 2) increased significantly. NO inhibitorinduced hypertension caused no changes in ANP concentrations. However, the ACEI and ARB had a direct effe...

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Section: Discussionmentioning

confidence: 99%

Effectiveness of Angiotensin-Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker on Atrial Natriuretic Peptide

Sata

Tanaka

Suzuki

et al. 2003

Circ J

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“…13,59 Furthermore, chronic NO blockade induced structural and functional alterations of the heart. [60][61][62][63] Finally, NOS inhibition deteriorated liver function in a model of alcohol-induced liver disease. 64 In conclusion, administration of L-NMMA, a NOS inhibitor, to patients with compensated cirrhosis, portal hypertension, and hyperdynamic circulation, corrected the altered systemic hemodynamics and improved renal hemodynamics and sodium excretion.…”

Section: Discussionmentioning

confidence: 99%

Hemodynamic, Renal, and Endocrine Effects of Acute Inhibition of Nitric Oxide Synthase in Compensated Cirrhosis

et al. 2001

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To assess whether an increased production of nitric oxide is involved in the circulatory and renal alterations of cirrhosis, we evaluated systemic hemodynamics (echocardiography), renal hemodynamics, and sodium handling (lithium clearance method), plasma renin activity (PRA), aldosterone (PAC), and norepinephrine in 7 patients (3 men, mean age 65 ؎ 2 years) with compensated cirrhosis, portal hypertension, and hyperdynamic circulation during intravenous N Gmonomethyl-L-arginine (L-NMMA) (3 mg/kg bolus plus 0.05 mg/kg ⅐ min for 120 minutes) or placebo (the vehicle) in a randomized, placebo-controlled, crossover study. Administration of L-NMMA resulted in significant reductions in plasma and urinary nitrite levels and plasma cyclic guanosine monophosphate (cGMP), indicating effective inhibition of nitric oxide synthase. L-NMMA also significantly reduced cardiac index (؊13%) and increased systemic vascular resistance (؉26%), arterial pressure (؉9%), renal blood flow (؉12%), glomerular filtration rate (؉12%), and sodium excretion (؉25%). Changes in sodium excretion were caused by both enhanced filtered sodium load and reduced sodium reabsorption in the proximal tubule. Plasma norepinephrine significantly decreased in response to L-NMMA, and there was a trend for reductions in PRA and PAC. Placebo had no appreciable effect on any of the measured parameters. These results indicate that in patients with compensated cirrhosis, portal hypertension and hyperdynamic circulation inhibition of nitric oxide synthase corrects the altered systemic hemodynamics and improves re- Patients with cirrhosis and portal hypertension eventually develop a hyperdynamic circulation, with high cardiac output, reduced systemic vascular resistance, and a trend towards arterial hypotension. 1 This abnormality, that contributes to worsen portal hypertension and plays a major role in the pathogenesis of other complications, including ascites and renal failure, has been related to peripheral arterial vasodilation, mainly occurring in the splanchnic circulation. 2 The cause(s) and mechanism(s) of arterial vasodilation are still unknown, but available evidence suggests that an increased synthesis of nitric oxide (NO) participates in the pathogenesis of the altered systemic hemodynamics in cirrhosis. 3,4 Animals with experimental cirrhosis have increased expression of nitric oxide synthase (NOS) and increased synthesis of NO in the vasculature. 5-9 They also have impaired response to vasoconstrictors in isolated aortic rings or splanchnic vasculature preparations, which is reversed by NOS inhibitors, 10,11 and increased pressor response to systemic administration of NOS inhibitors. 12,13 In addition, normalization of NO production by low-dose N G -nitro-L-arginine methyl ester, a NOS inhibitor, corrected the altered systemic hemodynamics, normalized the activity of the main vasoconstricting and sodiumretaining systems, 14 and improved renal sodium and water excretion in cirrhotic rats with ascites. 15 Evidence of an increased synthesis of NO has also ...

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“…We observed a similar blood pressure reduction after lisinopril administration and no additive effect with the combination therapy. It is well-known that inhibition of the RAS system is able to normalize arterial blood pressure in hypertensive heart disease both in spontaneously hypertensive rats (Brilla et al, 1996) and in rats with L-NNA-induced hypertension (Verhagen et al, 2000). Additionally, ACEinhibitors inhibit the degradation of bradykinin, thereby increasing their blood pressure lowering effects (Grafe et al, 1993).…”

Section: Oral Sts Attenuated L-nna-induced Hypertensionmentioning

confidence: 99%

Cardiac Protection by Oral Sodium Thiosulfate in a Rat Model of L-NNA-Induced Heart Disease

et al. 2021

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Hypertension contributes to cardiac damage and remodeling. Despite the availability of renin-angiotensin system inhibitors and other antihypertensive therapies, some patients still develop heart failure. Novel therapeutic approaches are required that are effective and without major adverse effects. Sodium Thiosulfate (STS), a reversible oxidation product of hydrogen sulfide (H2S), is a promising pharmacological entity with vasodilator and anti-oxidant potential that is clinically approved for the treatment of calciphylaxis and cyanide poisoning. We hypothesized that Sodium Thiosulfate improves cardiac disease in an experimental hypertension model and sought to investigate its cardioprotective effects by direct comparison to the ACE-inhibitor lisinopril, alone and in combination, using a rat model of chronic nitric oxide (NO) deficiency. Systemic nitric oxide production was inhibited in Sprague Dawley rats by administering N-ω-nitro-l-arginine (L-NNA) with the food for three weeks, leading to progressive hypertension, cardiac dysfunction and remodeling. We observed that STS, orally administered via the drinking water, ameliorated L-NNA-induced heart disease. Treatment with STS for two weeks ameliorated hypertension and improved systolic function, left ventricular hypertrophy, cardiac fibrosis and oxidative stress, without causing metabolic acidosis as is sometimes observed following parenteral administration of this drug. STS and lisinopril had similar protective effects that were not additive when combined. Our findings indicate that oral intervention with a H2S donor such as STS has cardioprotective properties without noticeable side effects.

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Unchanged cardiac angiotensin II levels accompany losartan-sensitive cardiac injury due to nitric oxide synthase inhibition

Cited by 14 publications

References 33 publications

Effectiveness of Angiotensin-Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker on Atrial Natriuretic Peptide

Effectiveness of Angiotensin-Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker on Atrial Natriuretic Peptide

Hemodynamic, Renal, and Endocrine Effects of Acute Inhibition of Nitric Oxide Synthase in Compensated Cirrhosis

Cardiac Protection by Oral Sodium Thiosulfate in a Rat Model of L-NNA-Induced Heart Disease

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