Angiotensin II subtype AT1 receptor blockade prevents hypertension and renal insufficiency induced by chronic NO-synthase inhibition in rats

Hropot, M.; Langer, Karl; Wiemer, Gabriele; Grötsch, H.; Linz, Wolfgang

doi:10.1007/s00210-002-0682-3

Cited by 16 publications

(9 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This observation agrees with the findings that the inhibition of NOS by L-NAME in cultured hepatocytes increases the intracellular levels of glycogen (Donato et al 2001), and that NO donors such as S-nitroso-N-acetylpenicillamine (SNAP) inhibit the biosynthesis of glycogen (Sprangers et al 1998) and may cause discreet inhibition of glycogenolysis stimulated by glucagon (Brass and Vetter 1993). In contrast, Hropot et al (2003) have observed that treatment of rats with L-NAME (25 mg/rat per day for 6 weeks) decreases the content of glycogen, ATP, and creatine phosphate in cardiac tissue, and Kitano et al (2002) have reported that NO has little effect on glycogen synthesis by hepatocytes. The inhibition of glycogen synthesis by NO involves a reduction in glycogen synthase activity (Sprangers et al 1998) and in the expres- Fig.…”

Section: Discussionsupporting

confidence: 89%

“…This finding indicates that the RAS, which is activated in this model (Zatz and Baylis 1998), modulates the accumulation of glycogen, since the inhibition of ACE (leading to reduced angiotensin II formation) and the blockade of AT 1 receptors (preventing the binding of angiotensin II) protected against glycogen accumulation. The mechanism by which this occurs is unclear, since angiotensin II generally stimulates glycogenolysis (Machado et al 1995;Henriksen and Jacob 2003), and in cardiac tissue, ACE inhibition (Hropot et al 1994) and AT 1 blockade (Hropot et al 2003) protect against the decrease in glycogen, ATP, and creatine phosphate seen following treatment with L-NAME.…”

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Hepatic morphological alterations, glycogen content and cytochrome P450 activities in rats treated chronically with Nω-nitro-L-arginine methyl ester (L-NAME)

et al. 2007

View full text Add to dashboard Cite

Chronic treatment of rats with N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) biosynthesis, results in hypertension mediated partly by enhanced angiotensin-I-converting enzyme (ACE) activity. We examined the influence of L-NAME on rat liver morphology, on hepatic glycogen, cholesterol, and triglyceride content, and on the activities of the cytochrome P450 isoforms CYP1A1/2, CYP2B1/2, CYP2C11, and CYP2E1. Male Wistar rats were treated with L-NAME (20 mg/rat per day via drinking water) for 2, 4, and 8 weeks, and their livers were then removed for analysis. Enzymatic induction was produced by treating rats with phenobarbital (to induce CYP2B1/2), beta-naphthoflavone (to induce CYP1A1/2), or pyrazole (to induce CYP2E1). L-NAME significantly elevated blood pressure; this was reversed by concomitant treatment with enalapril (ACE inhibitor) or losartan (angiotensin II AT(1) receptor antagonist). L-NAME caused vascular hypertrophy in hepatic arteries, with perivascular and interstitial fibrosis involving collagen deposition. Hepatic glycogen content also significantly increased. L-NAME did not affect fasting glucose levels but significantly reduced insulin levels and increased the insulin sensitivity of rats, based on an intraperitoneal glucose tolerance test. Immunoblotting experiments indicated enhanced phosphorylation of protein kinase B and of glycogen synthase kinase 3. All these changes were reversed by concomitant treatment with enalapril or losartan. L-NAME had no effect on hepatic cholesterol or triglyceride content or on the basal or drug-induced activities and protein expression of the cytochrome P450 isoforms. Thus, the chronic inhibition of NO biosynthesis produced hepatic morphological alterations and changes in glycogen metabolism mediated by the renin-angiotensin system. The increase in hepatic glycogen content probably resulted from enhanced glycogen synthase activity following the inhibition of glycogen synthase kinase 3 by phosphorylation.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 96%

Hepatic morphological alterations, glycogen content and cytochrome P450 activities in rats treated chronically with Nω-nitro-L-arginine methyl ester (L-NAME)

et al. 2007

View full text Add to dashboard Cite

show abstract

“…The inhibition of the NO synthesis results in an imbalance between the renin-angiotensin system (RAS) and the NO system in favor of the RAS; thus the effects of ANG II may prevail (20,30). A substantial body of work has shown that central or peripheral blockade of NO synthesis potentiates or prolongs the pressor response to ANG II (9,28,31,33), upregulates AT 1 expression, and activates cardiovascular angiotensin-converting enzyme (49).…”

Section: Discussionmentioning

confidence: 99%

Protective actions of estrogen on angiotensin II-induced hypertension: role of central nitric oxide

Xue¹,

Singh²,

Guo³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

.-The present study tested the hypotheses that 1) nitric oxide (NO) is involved in attenuated responses to ANG II in female mice, and 2) there is differential expression of neuronal NO synthase (nNOS) in the subfornical organ (SFO) and paraventricular nucleus (PVN) in response to systemic infusions of ANG II in males vs. females. Aortic blood pressure (BP) was measured in conscious mice with telemetry im-), an inhibitor of NOS, was administrated into the lateral cerebral ventricle for 14 days before and during ANG II pump implantation. Central infusion of L-NAME augmented the pressor effects of systemic ANG II in females (⌬21.5 Ϯ 2.2 vs. ⌬9.2 Ϯ 1.5 mmHg) but not in males (⌬29.4 Ϯ 2.5 vs. ⌬30.1 Ϯ 2.5 mmHg). Central administration of, a selective nNOS inhibitor, also significantly potentiated the increase in BP induced by ANG II in females (⌬17.5 Ϯ 3.2 vs. ⌬9.2 Ϯ 1.5 mmHg). In gonadectomized mice, central L-NAME infusion did not affect the pressor response to ANG II in either males or females. Ganglionic blockade after ANG II infusion resulted in a greater reduction in BP in central L-NAME-or L-VNIO-treated females compared with control females. Western blot analysis of nNOS protein expression indicated that levels were ϳ12-fold higher in both the SFO and PVN of intact females compared with those in intact males. Seven days of ANG II treatment resulted in a further increase in nNOS protein expression only in intact females (PVN, to ϳ51-fold). Immunohistochemical studies revealed colocalization of nNOS and estrogen receptors in the SFO and PVN. These results suggest that NO attenuates the increase in BP induced by ANG II through reduced sympathetic outflow in females and that increased nNOS protein expression associated with the presence of female sex hormones plays a protective role against ANG II-induced hypertension in female mice. sex hormone; nitric oxide/nitric oxide synthase; blood pressure NITRIC OXIDE (NO) and angiotensin II (ANG II) are important agents that regulate arterial blood pressure (BP). Vasoconstriction produced by sympathoexcitatory effects contributes to ANG II-induced pressor responses (13, 17). Conversely, NO has a hypotensive action via vasodilation and sympathoinhibition (36, 39). It has been shown that interactions between ANG II and NO occur in a variety of tissues, including the central nervous system (CNS) (40, 58). For example, microinjection of either an NO synthase (NOS) inhibitor or ANG II into the lateral ventricle or the paraventricular nucleus (PVN) increases the discharge of renal sympathetic nerves and elevates arterial BP and heart rate (HR) (25, 28, 52). Central or peripheral blockade of NOS potentiates or prolongs the pressor response to ANG II (9, 31). Conversely, overexpression of neuronal NOS (nNOS) within the PVN by adenoviral gene transfer significantly attenuates ANG II pressor responses (28).There is evidence from human and animal studies that hypertension is delayed and attenuated in females compared with males (11). Previous studies from our laboratory (54) have sh...

show abstract

“…Hypertension is associated with functional and structural alterations in both conduit and resistance arteries, which may be the result of long-lasting hypertension [3]. Treatment with nitric oxide synthase (NOS) inhibitor N G -nitro-Larginine methyl ester (L-NAME) induces hypertension and renal insufficiency in the rat [4]. The link between the kidney and hypertension is considered as a villain-victim relationship [5,6].…”

Section: Introductionmentioning

confidence: 99%

Protein kinase Cβ mediates downregulated expression of glucagon-like peptide-1 receptor in hypertensive rat renal arteries

Liu

Gao

et al. 2015

Journal of Hypertension

View full text Add to dashboard Cite

show abstract

Angiotensin II subtype AT1 receptor blockade prevents hypertension and renal insufficiency induced by chronic NO-synthase inhibition in rats

Cited by 16 publications

References 28 publications

Hepatic morphological alterations, glycogen content and cytochrome P450 activities in rats treated chronically with Nω-nitro-L-arginine methyl ester (L-NAME)

Hepatic morphological alterations, glycogen content and cytochrome P450 activities in rats treated chronically with Nω-nitro-L-arginine methyl ester (L-NAME)

Protective actions of estrogen on angiotensin II-induced hypertension: role of central nitric oxide

Protein kinase Cβ mediates downregulated expression of glucagon-like peptide-1 receptor in hypertensive rat renal arteries

Contact Info

Product

Resources

About