Hipertensión arterial mal controlada secundaria a quiste vascular suprarenal / Vascular adrenal cyst causing difficult to control high blood pressure

La hipertensión arterial supone un importante problema de salud pública en los países desarrollados. Las masas suprarrenales pueden pasar desapercibidas, ya que no son lesiones frecuentes y no producen síntomas o no se les atribuyen directamente. Estas circunstancias hacen que sea fundamental la actuación médica multidisciplinar. Comunicamos el caso de una mujer de 72 años, hipertensa mal controlada de años de evolución (3 fármacos antihipertensivos, sin alcanzar la tensión arterial en rango de normalidad), remitida por hallazgo incidental de lesión retroperitoneal derecha. Se diagnostica de quiste de origen suprarrenal posiblemente responsable del cuadro hipertensivo. Realizamos revisión de la literatura analizando diferentes actitudes diagnósticas y terapéuticas. Tras adrenalectomía por abordaje laparoscópico, conseguimos estabilizar a la paciente en cifras de tensión arterial dentro de la normalidad. La integración coordinada de servicios médicos y quirúrgicos es clave para el manejo de situaciones clínicas poco frecuentes. La cirugía laparoscópica constituye el tratamiento de elección en la enfermedad retroperitoneal (AU)

Hypertension is a prevalent disease in developed countries. Adrenal masses, and especially adrenal cysts, are a rare and usually asymptomatic finding, which can go unnoticed or be detected as incidental findings in imaging tests. These circumstances make the multidisciplinary approach mandatory. The case is presented on a 72 year-old woman with uncontrolled high blood pressure referred to the Urology Department due to the incidental finding of a right retroperitoneal mass. A functional and imaging study was performed, establishing a diagnosis of adrenal cyst causing hypertensive symptoms. A literature search was performed in order to assess diagnostic and therapeutic approaches. With the diagnosis of adrenal cyst causing uncontrolled high blood pressure, a right laparoscopic adrenalectomy was performed. After surgery the patient has maintained blood pressure within the normal range. A multidisciplinary approach is necessary for the management of rare diseases. The surgical approach, if possible, should be laparoscopic (AU)

Obligatory Metabolism of Angiotensin II to Angiotensin III for Zona Glomerulosa Cell-Mediated Relaxations of Bovine Adrenal Cortical Arteries.

Hyperaldosteronism is associated with hypertension, cardiac hypertrophy, and congestive heart failure. Steroidogenic factors facilitate aldosterone secretion by increasing adrenal blood flow. Angiotensin (Ang) II decreases adrenal vascular tone through release of zona glomerulosa (ZG) cell-derived vasodilatory eicosanoids. However, ZG cell-mediated relaxation of bovine adrenal cortical arteries to Ang II is not altered by angiotensin type 1 or 2 receptor antagonists. Because traditional Ang II receptors do not mediate these vasorelaxations to Ang II, we investigated the role of Ang II metabolites. Ang III was identified by liquid chromatography-mass spectrometry as the primary ZG cell metabolite of Ang II. Ang III stimulated ZG cell-mediated relaxation of adrenal arteries with greater potency than did Ang II. Furthermore, ZG cell-mediated relaxations of adrenal arteries by Ang II were attenuated by aminopeptidase inhibition, and Ang III-stimulated relaxations persisted. Ang IV had little effect compared with Ang II. Moreover, ZG cell-mediated relaxations of adrenal arteries by Ang II were attenuated by an Ang III antagonist but not by an Ang (1-7) antagonist. In contrast, Ang II and Ang III were equipotent in stimulating aldosterone secretion from ZG cells and were unaffected by aminopeptidase inhibition. Additionally, aspartyl and leucyl aminopeptidases, which convert Ang II to Ang III, are the primary peptidase expressed in ZG cells. This was confirmed by enzyme activity. These data indicate that intra-adrenal metabolism of Ang II to Ang III is required for ZG cell-mediated relaxations of adrenal arteries but not aldosterone secretion. These studies have defined an important role of Ang III in the adrenal gland.

Effects of metformin on the adrenal cortex of androgenized rats.

OBJECTIVE: To evaluate the sex steroid profile and histomorphometry of the adrenal cortical zones of androgenized rats (wistar) with polycystic ovary syndrome treated with metformin. STUDY DESIGN: Thirty animals were divided into three groups: GC (regular estrous cycle), GPE (permanent estrus), and GPEM (permanent estrus + metformin 28 mg/kg for 50 days). At the end of this period, blood was collected for hormone measurement. The width of the adrenal cortical zones and the nuclear volumes were analyzed by histomorphometry. The ANOVA test was used in the statistical analysis. RESULTS: The adrenal glands of the androgenized animals were larger and more intensely vascularized than those of the other groups. The concentration of androstenedione in GPE was higher than that in the other groups (0.4 ± 0.1*>= 0.2 ± 0.1 = 0.2 ± 01, *p < 0.05). The width of the zona glomerulosa and of the zona reticularis and their nuclear volumes were greater in GPE compared to those of the other groups (GPE* > GPEM = GC, *p < 0.05). CONCLUSION: Metformin treatment may decrease the serum levels of androstenedione as well as the width and the nuclear volumes of the zona glomerulosa and of the zona reticularis in androgenized animals.

Correlation between selected angiogenic markers and prognosis in pediatric adrenocortical tumors: Angiogenic markers and prognosis in pediatric ACTs.

BACKGROUND/PURPOSE: Pediatric adrenocortical tumor (ACT) remains a challenging disease. Tumor weight and disease stage are still the most used indicators to prognosis and guidance of clinical decisions. Histology has not added meaningful data for risk stratification and management. ACT is metabolically active, highly vascularized, locally invasive and has the propensity to produce distant metastasis. Our objective was to correlate the expression of vascular endothelial growth factor (VEGF) and intratumoral microvessel density (MVD) with clinical and prognostic aspects in pediatric ACT. PROCEDURE: In 27 tumors, immunohistochemical expression of VEGF, CD105 (endoglin) and CD34 was analyzed. MVD was determined by CD34 and CD105 antibodies. MVD and VEGF expression was correlated with clinical characteristics and outcome. Normal pediatric glands were used as controls. RESULTS: Endoglin MVD was significantly higher and CD34 MVD was significantly lower in ACT than control. The VEGF expression did not differ between groups. Cytoplasmic staining for endoglin was correlated with hypertension in ACT. Endoglin MVD greater than 1 mv/field, CD34 MVD less than 32 mv/field and VEGF expression levels above 4.8% were associated with clinical and biological indicators of poor prognosis. CONCLUSIONS: Endoglin and CD34 MVD values are potential histological markers to refine the histologic classification of pediatric ACT.

Diagnosis and management of primary aldosteronism: an updated review.

Primary aldosteronism (PA) is the most common secondary form of arterial hypertension, with a particularly high prevalence among patients with resistant hypertension. Aldosterone has been found to be associated with cardiovascular toxicity. Prolonged aldosteronism leads to higher incidence of cardiac events, glomerular hyperfiltration, and potentially bone/metabolic sequels. The wider application of aldosterone/renin ratio as screening test has substantially contributed to increasing diagnosis of PA. Diagnosis of PA consists of two phases: screening and confirmatory testing. Adrenal imaging is often inaccurate for differentiation between an adenoma and hyperplasia, and adrenal venous sampling is essential for selecting the appropriate treatment modality. The etiologies of PA have two main subtypes: unilateral (aldosterone-producing adenoma) and bilateral (micro- or macronodular hyperplasia). Aldosterone-producing adenoma is typically managed with unilateral adrenalectomy, while bilateral adrenal hyperplasia is amenable to pharmacological approaches using mineralocorticoid antagonists. Short-term treatment outcome following surgery is determined by factors such as preoperative blood pressure level and hypertension duration, but evidence regarding long-term treatment outcome is still lacking. However, directed treatments comprising of unilateral adrenalectomy or mineralocorticoid antagonists still potentially reduce the toxicities of aldosterone. Utilizing a physician-centered approach, we intend to provide up-dated information on the etiology, diagnosis, and the management of PA.

Liquid chromatography-tandem mass spectrometry analysis of human adrenal vein 19-carbon steroids before and after ACTH stimulation.

CONTEXT: A broad analysis of adrenal gland-derived 19-carbon (C19) steroids has not been reported. This is the first study that uses liquid chromatography-tandem mass spectrometry to quantify 9 C19 steroids (androgens and their precursors), estrone, and estradiol in the adrenal vein (AV) of women, before and after ACTH stimulation. OBJECTIVE: The objective of this study was to define the adrenal androgen metabolome in women before and after ACTH infusion. DESIGN: This was a retrospective study. PATIENTS: Seven women, aged 50.4 ± 5.4 years, with suspected diagnosis of an adrenal aldosterone-producing adenoma were included in the study. METHODS: AV and iliac serum samples were collected before and after administration of ACTH (15 minutes). AV samples were analyzed using for concentrations of 9 unconjugated C19 steroids, estrone, and estradiol. Dehydroepiandrosterone sulfate (DHEA-S) was quantified by radioimmunoassay. RESULTS: AV levels of DHEA-S were the highest among the steroids measured. The most abundant unconjugated C19 steroids in AV were 11ß-hydroxyandrostenedione (11OHA), dehydroepiandrosterone (DHEA), and androstenedione (A4). ACTH significantly increased the adrenal output of 9 of the 12 steroids that were measured. ACTH increased the mean AV concentration of DHEA-S by 5-fold, DHEA by 21-fold, A4 by 7-fold, and 11OHA by 5-fold. 11ß-Hydroxytestosterone and testosterone were found to be potent androgen receptor agonists when tested with an androgen-responsive cell reporter model. CONCLUSION: The current study indicates that the adrenal gland secretes primarily 3 weak androgens, namely DHEA, 11OHA, and A4. Active androgens, including testosterone and 11ß-hydroxytestosterone, are also produced but to a lesser degree.

Control of CYP11B2/CYP11B1 expression ratio and consequences for the zonation of the adrenal cortex.

Access of corticotropin to glucocorticoid synthesis in adrenocortical cells is provided by the expression of the ACTH receptor (MC2R). Activation of the MC2R increases stimulatory G-protein, adenylyl cyclase, and protein kinase A (PKA) activities. Furthermore, PKA phosphorylates transcription factors that have a stimulating effect on glucocorticoid synthesis. Sensitivity of adrenocortical cells to renin/angiotensin-2 is conferred by the expression of the inhibitory G-protein-linked angiotensin-2 type 1 receptor (AT1R) that additionally associates to the phospholipase C-activating G-protein q. The AT1R is connected to the adrenal potassium sensory system and regulates calcium influx as well as phospholipase C-ß (PLC-ß) and thus calmodulin kinase-dependent transcription of steroidogenic enzymes. While AT1R signaling suppresses the influence of corticotropin on the generation of cyclic adenosine monophosphate, the expression of the AT1R and its associated enzyme activities are under the control of glucocorticoids. Thus, dominance of one of the two signaling pathways is dependent on two factors: the extracellular concentration of their ligands and the products of their signaling pathways. These findings are in favor of the hypothesis that the centripetal blood flow through the adrenal gland builds up a glucocorticoid gradient creating a morphogenetic field along which adrenal cortical cells adopt different functional states, leading to the typical zonation of the adrenal cortex.

A clinical prediction score to diagnose unilateral primary aldosteronism.

CONTEXT: Adrenal venous sampling is recommended to assess whether aldosterone hypersecretion is lateralized in patients with primary aldosteronism. However, this procedure is invasive, poorly standardized, and not widely available. OBJECTIVE: Our goal was to identify patients' characteristics that can predict unilateral aldosterone hypersecretion in some patients who could hence bypass adrenal venous sampling before surgery. DESIGN AND SETTING: A cross-sectional diagnostic study was performed from February 2009 to July 2010 at a single center specialized in hypertension care. PATIENTS: A total of 101 consecutive patients with primary aldosteronism who underwent adrenal venous sampling participated in the study. The autonomy of aldosterone hypersecretion was assessed with the saline infusion test. INTERVENTION: Adrenal venous sampling was performed without ACTH infusion but with simultaneous bilateral sampling. MAIN OUTCOME MEASURES: Variables independently associated with a lateralized adrenal venous sampling in multivariate logistic regression were used to derive a clinical prediction rule. RESULTS: Adrenal venous sampling was successful in 87 patients and lateralized in 49. All 26 patients with a typical Conn's adenoma plus serum potassium of less than 3.5 mmol/liter or estimated glomerular filtration rate of at least 100 ml/min/1.73 m2 (or both) had unilateral primary aldosteronism; this rule had 100% specificity (95% confidence interval, 91-100) and 53% sensitivity (95% confidence interval, 38-68). CONCLUSIONS: If our results are validated on an independent sample, adrenal venous sampling could be omitted before surgery in patients with a typical Conn's adenoma if they meet at least one of two supplementary biochemical characteristics (serum potassium<3.5 mmol/liter or estimated glomerular filtration rate ≥100 ml/min/1.73 m2).

Age-dependent renal cortical microvascular loss in female mice.

Renal function and blood flow decline during aging in association with a decrease in the number of intrarenal vessels, but if loss of estrogen contributes to this microvascular, rarefaction remains unclear. We tested the hypothesis that the decreased renal microvascular density with age is aggravated by loss of estrogen. Six-month-old female C57/BL6 mice underwent ovariectomy (Ovx) or sham operation and then were allowed to age to 18-22 mo. Another comparable group was replenished with estrogen after Ovx (Ovx+E), while a 6-mo-old group served as young controls. Kidneys were then dissected for evaluation of microvascular density (by micro-computed tomography) and angiogenic and fibrogenic factors. Cortical density of small microvessels (20-200 µm) was decreased in all aged groups compared with young controls (30.3 ± 5.8 vessels/mm², P < 0.05), but tended to be lower in sham compared with Ovx and Ovx+E (9.9 ± 1.7 vs. 17.2 ± 4.2 and 18 ± 3.0 vessels/mm², P = 0.08 and P = 0.02, respectively). Cortical density of larger microvessels (200-500 µm) decreased only in aged sham (P = 0.04 vs. young control), and proangiogenic signaling was attenuated. On the other hand, renal fibrogenic mechanisms were aggravated in aged Ovx compared with aged sham, but blunted in Ovx+E, in association with downregulated transforming growth factor-ß signaling and decreased oxidative stress in the kidney. Therefore, aging induced in female mice renal cortical microvascular loss, which was likely not mediated by loss of endogenous estrogen. However, estrogen may play a role in protecting the kidney by decreasing oxidative stress and attenuating mechanisms linked to renal interstitial fibrosis.

The cortisol awakening response in context.

The cortisol awakening response (CAR) is a crucial point of reference within the healthy cortisol circadian rhythm, with cortisol secretion typically peaking between 30 and 45 min post awakening. This chapter reviews the history of investigation into the CAR and highlights evidence that its regulation is relatively distinct from cortisol secretion across the rest of the day. It is initiated by awakening, under the influence of the hypothalamic suprachiasmatic nucleus, and "fine tuned" by a direct neural input to the adrenal cortex by the sympathetic nervous system. This chapter also examples the CAR in relation to other awakening-induced processes, such as restoration of consciousness, attainment of full alertness, changes in other hormones, changes in the balance of the immune system, and mobilization of the motor system, and speculates that there is a role for the CAR in these processes.

Morphological and microvascular changes of the adrenal glands in streptozotocin-induced long-term diabetic rats.

It has been known that diabetes mellitus is associated with hyperfunction of the adrenal gland. However, the structural changes of adrenal gland in diabetes have rarely been studied. The aims of this study were to investigate the morphological and microvascular alterations in streptozotocin (STZ)-induced long-term diabetic rats. Twelve male Sprague-Dawley rats were divided into diabetic (n=8) and control (n=4) groups. Each diabetic rat was induced by an intraperitoneal injection of STZ (60 mg/kg) in citrate buffer (pH 4.5). Control rats were intraperitoneally injected with the same amounts of the buffer. These animals were sacrificed at 20 weeks after the injections. The adrenal glands were processed for the morphological and microvascular studies by using conventional light microscopy (LM) and vascular corrosion cast technique combined with scanning electron microscopy (SEM), respectively. In the diabetic group, the cells in zona glomeruloza (ZG) became atrophied and the thickness of this zone was found to be less than that of the controls. In the zona fasciculata (ZF) and zona reticularis (ZR), the hypertrophic cells were investigated in both layers. The degenerated chromaffin and hypertrophic sympathetic ganglion cells in the adrenal medulla were observed. Also some degenerated ganglion cells were found. Additionally, lymphocyte infiltration, macrophages and amyloidosis were found in the adrenal medulla of long-term diabetic rats with renal failure. Under the SEM observation, the luminal diameters of capillaries in the diabetic group were dilated in all zones. In addition, these capillaries in the ZF and ZR were arranged in tortuous courses. This study demonstrates morphological and microvascular changes in the adrenal gland of diabetic rats which are in accordance with the hormonal changes reported by previous investigators.

Angiotensin II relaxations of bovine adrenal cortical arteries: role of angiotensin II metabolites and endothelial nitric oxide.

Angiotensin (Ang) II regulates adrenal steroidogenesis and adrenal cortical arterial tone. Vascular metabolism could decrease Ang II concentrations and produce metabolites with vascular activity. Our goals were to study adrenal artery Ang II metabolism and to characterize metabolite vascular activity. Bovine adrenal cortical arteries were incubated with Ang II (100 nmol/L) for 10 and 30 minutes. Metabolites were analyzed by mass spectrometry. Ang (1-7), Ang III, and Ang IV concentrations were 146+/-21, 173+/-42 and 58+/-11 pg/mg at 10 minutes and 845+/-163, 70+/-14, and 31+/-3 pg/mg at 30 minutes, respectively. Concentration-related relaxations of U46619-preconstricted cortical arteries to Ang II (maximum relaxation=29+/-3%; EC(50)=3.4 pmol/L) were eliminated by endothelium removal and inhibited by the NO synthase inhibitor, nitro-L-arginine (30 micromol/L; maximum relaxation=14+/-7%). Ang II relaxations were enhanced by the angiotensin type-1 receptor antagonist losartan (1 micromol/L; maximum relaxation=41+/-3%; EC(50)=11 pmol/L). Losartan-enhanced Ang II relaxations were inhibited by nitro-L-arginine (maximum relaxation=18+/-5%) and the angiotensin type-2 receptor antagonist PD123319 (10 micromol/L; maximum relaxation=27+/-5%). Ang (1-7) and Ang III caused concentration-related relaxations with less potency (EC(50)=43 and 24 nmol/L, respectively) but similar efficacy (maximum relaxations=39+/-3% and 48+/-5%, respectively) as losartan-enhanced Ang II relaxations. Ang (1-7) relaxations were inhibited by nitro-L-arginine (maximum relaxation=16+/-4%) and the Ang (1-7) receptor antagonist 7(D)-Ala-Ang (1-7) (1 micromol/L; maximum relaxation=10+/-3%) and eliminated by endothelium removal. Thus, Ang II metabolism by adrenal cortical arteries to metabolites with decreased vascular activity represents an inactivation pathway possibly decreasing Ang II presentation to adrenal steroidogenic cells and limits Ang II vascular effects.

[Morphometric parameters of rat adrenals in the dynamics of general hypothermia].

In this study, some morphometric parameters of adrenals in outbred albino male rats were compared in the dynamics of general hypothermia at the ambient temperature of -18 degrees C. It was shown that in the course of general hypothermia, the increase of blood vessel relative volume in zona reticularis and in adrenal medulla was accompanied by the augmentation of nucleus size of adrenocorticocytes (mainly in zona fasciculata). Zona fasciculata reacted with a significant increase of blood vessel relative volume during the 1st hour of cold exposure, henceforth the parameters remained unchanged. Blood vessel relative volume in the left adrenal was found to significantly exceed that in the right adrenal. In zona glomerulosa of the left adrenal, blood vessel relative volume was reduced, while that one in zona glomerulosa of the right adrenal remained unchanged during the whole experiment. Volume density of mitochondria in the endocrine cells of zona fasciculata was found to increase, this effect being more pronounced in the right adrenal as compared to the left one. In the cells of both glands, the volume density of lipid inclusions was gradually reduced, while the relative volume of nucleoli was variable and there were no statistically significant changes detected during the course of hypothermia.

Heterogeneity of capillary endothelial cells for basic fibroblast growth factor-induced paracrine signaling.

In this study, the authors isolated morphologically different capillary endothelial cells, designated as BCE-1 and BCE-2 cells, from bovine adrenal cortex. By a series of experiments involving proliferation, migration, and tubular-like structure formation assays, the authors found that the two BCE clones showed a clearly different response to basic fibroblast growth factor (bFGF). Similar to these results, the ERK-1/2 in the BCE-1 cells was phosphorylated by bFGF or vascular endothelial growth factor (VEGF), whereas that of the BCE-2 cells was phosphorylated only by VEGF. However, when the BCE-2 cells were transfected with FGF receptor 1 cDNA, the ERK-1/2 of these cells was phosphorylated by exogenous bFGF. Receptor binding experiments revealed that BCE-2 cells expressed high-affinity tyrosine-kinase FGF receptors approximately twofold less than BCE-1 cells. Transfection and receptor binding studies suggest a possibility that the poor response of the BCE-2 cells to exogenous bFGF is derived from the limitation of functional availability of high affinity FGF receptors. On the other hand, when both BCE clones were treated with anti-bFGF antibodies, basal formation of tubular-like structure in both clones were strongly inhibited, indicating that endogenous bFGF plays a role in in vitro angiogenesis of both BCE clones. Taken together, these data show that the isolated capillary endothelial cells are heterogeneous for paracrine but not autocrine bFGF signaling, and suggest that the diversity of capillary endothelial cells can occur by angiogenic factors, such as bFGF.

Pored domes in adrenocortical capillaries. An ultrastructural study in mammals.

The adrenocortical gland is one of the most vascularized organs of the mammalian body. It undergoes continuous morphological changes dynamically dependent upon special permeability conditions related to various physiological and physiopathological events. The adrenal cortex of different adult mammals (3 pigs, 2 mice, 3 sheep) was studied by means of scanning (SEM) and transmission (TEM) electron microscopy. As seen by SEM it is formed of polyhedral cells which delimit a characteristic continuous labyrinth system of intercellular lacunae occupied by sinusoid-like capillaries. The capillary wall is fenestrated and is lined by flattened endothelial cells with their nuclear part bulging into the capillary lumen. The fenestrae are round or oval pores measuring 50-100 nm in diameter. They are usually clustered to form sieve plates and characteristically present a thin membranous diaphragm. Irregular microelevations and dome-like projections are often seen. These structures are made of thin cytoplasmic plates interrupted by numerous small pores which show a sieve plate profile. The pored-domes on the nuclear portion seem to be identical in structure to those found in the thinner endothelial part; some of them appear to detach from the endothelial cell. The pored-domes are structurally comparable to those reported both in the renal glomerular endothelium and in liver sinusoids. These endothelial structures may be an expression of the high rate of filtration of these tissues and may be also related to the final step of the replacement of the sieve plates during endothelial regeneration.

Mechanisms of histamine-induced relaxation in bovine small adrenal cortical arteries.

Adrenal steroidogenesis is closely correlated with increases in adrenal blood flow. Many reports have studied the regulation of adrenal blood flow in vivo and in perfused glands, but until recently few studies have been conducted on isolated adrenal arteries. The present study examined vasomotor responses of isolated bovine small adrenal cortical arteries to histamine, an endogenous vasoactive compound, and its mechanism of action. In U-46619-precontracted arteries, histamine (10(-9)-5 x 10(-6) M) elicited concentration-dependent relaxations. The relaxations were blocked by the H(1) receptor antagonists diphenhydramine (10 microM) or mepyramine (1 microM) (maximal relaxations of 18 +/- 6 and 22 +/- 6%, respectively, vs. 55 +/- 5% of control) but only partially inhibited by the H(2) receptor antagonist cimetidine (10 microM) and the H(3) receptor antagonist thioperamide (1 microM). Histamine-induced relaxations were also blocked by the nitric oxide synthase inhibitor N-nitro-L-arginine (L-NA, 30 microM; maximal relaxation of 13 +/- 7%) and eliminated by endothelial removal or L-NA combined with the cyclooxgenase inhibitor indomethacin (10 microM). In the presence of adrenal zona glomerulosa (ZG) cells, histamine did not induce further relaxations compared with histamine alone. Histamine (10(-7)-10(-5) M) concentration-dependently increased aldosterone production by adrenal ZG cells. Compound 48/80 (10 microg/ml), a mast cell degranulator, induced significant relaxations (93 +/- 0.6%), which were blocked by L-NA plus indomethacin or endothelium removal, partially inhibited by the combination of the H(1), H(2), and H(3) receptor antagonists, but not affected by the mast cell stabilizer sodium cromoglycate (1 mM). These results demonstrate that histamine causes direct relaxation of small adrenal cortical arteries, which is largely mediated by endothelial NO and prostaglandins via H(1) receptors. The potential role of histamine in linking adrenal vascular events and steroid secretion requires further investigation.

Angiotensin II dilates bovine adrenal cortical arterioles: role of endothelial nitric oxide.

Adrenal steroidogenesis is modulated by humoral and neuronal factors and blood flow. Angiotensin II (AII) stimulates adrenal cortical aldosterone and cortisol production and medullary catecholamine release. However, AII regulation of adrenal vascular tone has not been characterized. We examined the effect of AII on diameters of cannulated bovine adrenal cortical arteries. Cortical arteries (average internal diameter = 230 microm) were constricted with U46619 and concentration-diameter responses to AII (10(-13) to 10(-8) mol/liter) were measured. In endothelium-intact arteries, AII induced dilations at low concentrations (maximum dilation = 25 +/- 6% at 10(-10) mol/liter) and constrictions at high concentrations (maximum constriction = 25 +/- 18% at 10(-8) mol/liter). AII constrictions were blocked by the angiotensin type 1 (AT1) receptor antagonist, losartan (10(-6) mol/liter). AII dilations were enhanced by losartan (maximal dilation = 48 +/- 8%), abolished by endothelial cell removal or N-nitro-L-arginine (L-NA, 3 x 10(-5) mol/liter) and inhibited by the angiotensin type 2 (AT2) receptor antagonist, PD123319 (10(-6) mol/liter, maximal dilation = 18 +/- 4%). In a 4,5-diaminofluorescein diacetate nitric oxide (NO) assay of isolated cortical arteries, AII stimulated NO production, which was abolished by PD123319, L-NA, or endothelial cell removal. Western immunoblot of arterial homogenates and endothelial and zona glomerulosa cell lysates revealed 48-kD and 50-kD bands corresponding to AT1 and AT2 receptors, respectively, in all three and a 140-kD band corresponding to endothelial NO synthase in endothelial cells and arteries. Our results demonstrate that AII stimulates adrenal cortical arterial dilation through endothelial cell AT2 receptor activation and NO release and AT1 receptor-dependent constriction.