Chronic administration of nitric oxide reduces angiotensin II receptor type 1 expression and aldosterone synthesis in zona glomerulosa cells

Abstract

surface-enhanced Raman scattering ANGIOTENSIN II (ANG II) stimulates aldosterone secretion and contraction of vascular smooth muscle (7,18,28) and contributes to the regulation of systemic blood pressure. Two ANG II receptor subtypes, AT1 and AT2, have been cloned and characterized (5, 17, 18). These receptors are seven-transmembrane G protein-coupled receptors. ANG II receptors are densely located in the adrenal cortex, particularly in zona glomerulosa (ZG) cells (12,14,33). Binding of ANG II to AT1 receptors stimulates the synthesis of aldosterone. Aldosterone is released into the circulation, acts at the kidney tubule, and enhances sodium resorption and potassium excretion (25). The absorbed sodium contributes to enhance water resorption in the kidney. This results in the increase in extracellular fluid volume and subsequent increase in arterial pressure.Inhibition of nitric oxide (NO) synthase with nitro-L-arginine methyl ester (L-NAME) resulted in an increase in cellular expression of ANG II receptors in adrenal glands and smooth muscle cells (3,16,19,34,38). Administration of L-NAME to rats increased plasma aldosterone and AT1 receptor mRNA and protein in adrenal homogenates (38). Chronic administration of L-NAME to normal rats also increased cardiac AT1 and AT2 receptor expression (19). Stimulation of vascular smooth muscle cells with S-nitroso-N-acetyl-DL-penicillamine, an NO donor, significantly decreased the receptor density (B max ) but did not affect the affinity (K d ) of ANG II (3). Chronic treatment of rat vascular smooth muscle cells with NO decreased the binding of ANG II through a guanylyl cyclase/cGMP-independent mechanism. It is not known whether NO affects the expression and localization of ANG II receptors in ZG cells. We (9, 10) previously showed that acute treatment with NO inhibited the ANG II-, 25-hydroxycholesterol-, and pregnenolone-stimulated aldosterone synthesis in ZG cells, and this mechanism is guanylyl cyclase/cGMP independent. NO inhibited aldosterone biosynthesis by binding steroidogenic enzymes. The sensitivity to NO inhibition was increased at low oxygen concentrations (9). These observations led us to examine the effects of chronic exposure of ZG cells to NO on the expression of AT1 receptors and aldosterone synthesis.Adrenal endothelial cells contain NO synthase and produce NO, whereas ZG cells do not (9). Thus endothelial cells are the major source of NO in the adrenal cortex. The adrenal gland is highly vascularized, so ZG cells are in close proximity to capillaries and endothelial cells (39). Thus ZG cells are chronically exposed to endothelial NO. ANG II stimulates endothelial NO release (11). In the presence of endothelial cells, ZG cells release less aldosterone in response to ANG II compared with ZG cells alone. This reduced aldosterone release can be reversed by NO synthase inhibitors. These studies indicate that endothelial NO can regulate aldosterone release from ZG cells.In this study, the effects of chronic NO administration on the expression and localization o...

Functional expression of the renin-angiotensin system in human podocytes

“…Immunostainings most often detected angiotensin receptors as intracellular clusters. Similar expression patterns of angiotensin receptors have also been recently shown in various other cell types (37,50).…”

NO Synthase Inhibition Increases Aldosterone in Humans

“…In this regard, NOS inhibition has been reported to increase renin activity 17 and to enhance Ang II type 1 receptor expression. 12,18 In the present study, there was no effect of L-NAME on PRA or Ang II concentrations. Whereas there was no relationship between Ang II concentrations and either PRA or aldosterone, indi- cating the limitation of circulating Ang II as a measure of local Ang II concentrations, L-NAME enhanced the relationship between aldosterone and PRA.…”

“…Because administration of the NOS precursor L-arginine can enhance eNOS function in some populations, 16 we studied the effect of L-NAME in the presence and absence of L-arginine. Because inhibition of NOS increases the activity of the renin-angiotensin-aldosterone system (RAAS), 12,17,18 whereas angiotensin-converting enzyme (ACE) inhibition increases eNOS, 19 we also determined the effect of L-NAME on circulating aldosterone concentrations in the presence and absence of the ACE inhibitor ramipril. …”

Effect of Melatonin on the Renin-Angiotensin-Aldosterone System in l-NAME-Induced Hypertension

“…Supposedly, increased number of AT1 receptor in the suprarenal gland may have counterbalanced the decreased level of Ang II regarding the aldosterone production in our experiment. Third, a number of papers indicate that NO inhibits aldosterone secretion in glomerulosa cells through a cGMP-independent mechanism [ 50 , 51 ], potentially via direct reduction of steroidogenesis in zona glomerulosa or by downregulation of AT1 receptors [ 52 ]. Indeed, l -NAME administration increased the level of aldosterone even 50-fold [ 53 ] independently on renin or Ang II level [ 54 ].…”