Need, readiness and opportunities for family HIV/AIDS intervention in China.
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Adolescent↗
Biomedical subjects
J Zhuo
Publications and source records attributed to J Zhuo.
Evaluation of metallothionein and p53 expression as potential prognostic markers for laryngeal squamous cell carcinoma.
The aim of the study was to determine the contribution of metallothionein (MT) and p53 expression in predicting laryngeal squamous cell carcinoma (SCC) recurrence. This was a retrospective study in which MT and p53 immunopositive staining in 32 laryngeal SCC paraffin-embedded sections, were correlated with clinical recurrence. Recurrence was observed in 8 cases with MT expression (42.1%) and 1 case with no expression (7.7%). Moderate and strong MT expression was associated with 14.3% and 58.3% recurrence, respectively. Recurrence was similar for both p53-negative (21.1%) and p53-positive (27.3%) groups. One third of the patients expressing both p53 and MT simultaneously had recurrence. Thus, the combined expression of p53 and MT did not improve the predictive value for recurrence compared to MT alone. MT over-expression may be an independent risk factor for laryngeal SCC recurrence.
Biomarkers, Tumor↗
Localization of angiotensin-converting enzyme in the human prostate: pathological expression in benign prostatic hyperplasia.
Benign prostatic hyperplasia (BPH) is the most common hyperplastic disease in man and it is characterized by increased cellular growth (stromal and epithelial hyperplasia) and enhanced local sympathetic tone, both of which are known to be augmented by activation of the renin-angiotensin system (RAS) in other tissues. Angiotensin-converting enzyme (ACE) is an integral component of the RAS that is responsible for the production of the active peptide angiotensin II from the inactive precursor angiotensin I. The present study was undertaken to map the anatomical localization of ACE protein and messenger ribonucleic acid (mRNA) in the normal human prostate and to establish whether their expression is pathologically altered in BPH. Human prostate samples were obtained at post-mortem and histologically defined as normal or hyperplastic. ACE protein binding/expression was determined by in vitro autoradiography and immunohistochemistry using the ACE-specific radioligand [125I]-MK351A and a mouse anti-ACE polyclonal antibody, respectively, whereas the spatiotemporal distribution of ACE mRNA was determined by in situ hybridization using 35S-labelled oligonucleotide probes. ACE protein was localized to the glandular epithelium in the human prostate. ACE binding and immunostaining were increased in BPH compared with normal (non-hyperplastic) prostate specimens [X-ray film autoradiography: normal 873+/-48 dpm/mm2 (n=8) vs. BPH 1631+/-274 dpm/mm2 (n=6), p<0.05; emulsion autoradiography: normal 3.1+/-0.5 grains/mm2 (n=6) vs. BPH 32.8+/-8.6 grains/mm2 (n=5), p<0.01]. ACE mRNA was also localized to glandular epithelial cells in the human prostate with a significant increase in ACE mRNA expression in BPH compared with the normal prostate [normal 11.04+/-2.03 grains/cell (n=220 cells total) vs. BPH 22.29+/-1.34 grains/cell (n=198 cells total), p<0.05]. The findings of the present study suggest that ACE is localized to the glandular epithelium of the human prostate and that its expression, at both protein and mRNA level, is aberrantly increased in BPH. These data support the concept that hyperactivity of the local RAS in the prostate may be involved in the pathogenesis of BPH.
Autoradiography↗
Localization and function of angiotensin AT1 receptors.
The distributions of angiotensin AT1 and AT2 receptors have been mapped by in vitro autoradiography throughout most tissues of many mammals, including humans. In addition to confirming that AT1 receptors occur in sites known to be targets for the physiologic actions of angiotensin, such as the adrenal cortex and medulla, renal glomeruli and proximal tubules, vascular and cardiac muscle and brain circumventricular organs, many new sites of action have been demonstrated. In the kidney, AT1 receptors occur in high density in renal medullary interstitial cells. The function of these cells, which span the interstitial space between the tubules and the vasa rectae, remains to be determined. Renal medullary interstitial cells possess receptors for a number of vasoactive hormones in addition to AT1 receptors and this, in concert with their anatomic location, suggests they may be important for the regulation of fluid reabsorption or renal medullary blood flow. In the heart, the highest densities of AT1 receptors occur in association with the conduction system and vagal ganglia. In the central nervous system, high AT1 receptor densities occur in many regions behind the blood-brain barrier, supporting a role for neurally derived angiotensin as a neuromodulator. The physiologic role of angiotensin in many of these brain sites remains to be determined. The AT2 receptor also has a characteristic distribution in several tissues including the adrenal gland, heart, and brain. The role of this receptor in physiology is being elucidated, but it appears to inhibit proliferation and to participate in development. Thus, receptor-binding studies, localizing the distribution of AT1 and AT2 receptors, provide many insights into novel physiologic roles of angiotensin.
Animals↗
The relationship of hepatitis B virus infection between adults and their children in Guangxi Province, China.
BACKGROUND/AIM: This study aimed to describe the seroepidemiology of hepatitis B virus (HBV) infection, with emphasis on transmission of HBV infection between adults and their children. METHODS: We analyzed the hepatitis sero-survey data collected from 2132 persons aged 1-59 years (624 families) in Guangxi Province, China, 1992. Blood was tested for the presence of the hepatitis B surface antigen (HBsAg), the antibody to hepatitis B core antigen (anti-HBc), and the antibody to hepatitis B surface antigen (anti-HBs). RESULTS: Of the 2132 persons surveyed, 119 (5.6%) reported receiving HBV vaccination. Among those persons who did not receive HBV vaccination, 19% were HBsAg positive (current HBV infection) and 57% had a past HBV infection (they were HBsAg negative and either anti-HBc positive or anti-HBs positive). Among 519 children aged 1-10 years who did not receive HBV vaccination, 21% had current HBV infection and 37% had past HBV infection. Among 289 children of both parents who were HBsAg negative, 16% had current HBV infection and 36% had past HBV infection. CONCLUSIONS: The high prevalence of community-acquired HBV infection in children and the low HBV vaccination coverage in Guangxi should alert public health agencies to re-examine their current policies for preventing HBV transmission.
Adolescent↗
Rat renomedullary interstitial cells possess bradykinin B2 receptors in vivo and in vitro.
1. Renomedullary interstitial cells (RMIC), abundant throughout the medulla of the kidney, have been demonstrated to have binding sites for many vasoactive peptides, including atrial natriuretic peptide, endothelin, angiotensin II and bradykinin (BK). These observations would support the hypothesis that interactions between RMIC and vasoactive peptides are important in the regulation of renal function. 2. We aimed to localize the BK B2 receptor binding site to RMIC in vivo and to also demonstrate that these receptors are biologically active in vitro. 3. The present study demonstrates BK B2 binding sites on RMIC of the inner stripe of the outer medulla and the inner medulla of the rat kidney in vivo. 4. We further demonstrate that the BK B2 radioligand [125I]-HPP-Hoe140 specifically bound to rat RMIC in vitro. In addition, reverse transcription-polymerase chain reaction detected the mRNA for the BK B2 receptor subtype in cell extracts. 5. For RMIC in vitro, cAMP levels were increased at 1 min and cGMP levels were increased at 2 min after treatment with 10(-10) and 10(-7) mol/L BK, respectively. Inositol 1,4,5-trisphosphate was increased at 10 s treatment with both 10(-6) and 10(-7) mol/L BK. 6. For RMIC in vitro, BK induced an increase in cell proliferation ([3H]-thymidine incorporation) and an increase in extracellular matrix synthesis (ECM; trans-[35S] incorporation), both effects mediated by BK B2 receptors. 7. We conclude that BK B2 receptors are present on RMIC both in vivo and in vitro. These receptors are coupled to intracellular second messenger systems and, in vitro, their stimulation results in cellular proliferation and synthesis of ECM.
Animals↗
Roles of AT1 and AT2 receptors in the hypertensive Ren-2 gene transgenic rat kidney.
Adult Ren-2 gene transgenic rats, TGR(mRen-2)27, exhibit elevated circulating and kidney angiotensin II (Ang II) levels in the presence of severe hypertension. The aim of this study was to examine whether AT1 and AT2 receptors in the kidney and renal hemodynamic and tubular responses to blockade of these receptors were altered in the Ren-2 gene transgenic rats during the maintenance phase of hypertension. Renal AT1 and AT2 receptors were mapped by in vitro autoradiography (n=8), and the effects of blockade of these receptors on mean arterial pressure (MAP), heart rate (HR), and renal cortical (CBF) and medullary blood flows (MBF) were studied in anaesthetized, adult age-matched male homozygous TGR rats (n=12) and Sprague-Dawley (SD) rats (n=7). TGR rats showed higher basal MAP (P<0.001), heart and kidney weight (P<0.001), plasma renin activity (P<0.05) and plasma Ang II level (P<0.05), and CBF (P<0.05) and MBF (P<0.05) than SD rats. AT1 receptor binding was significantly increased in the glomeruli, proximal tubules, and the inner stripe of the outer medulla of TGR rats (P<0.01), while the AT2 receptor binding was low at all renal sites of TGR and SD rats. Immunohistochemistry revealed that this increased AT1 receptor labeling occurred mainly in vascular smooth muscle layer of intrarenal blood vessels including afferent and efferent arterioles, juxtaglomerular apparatus, glomerular mesangial cells, proximal tubular cells, and renomedullary interstitial cells (RMICs) in the transgenic rats. Blockade of AT1 receptors with losartan in TGR rats markedly reduced MAP to the normotensive level (P<0.001) without altering HR. Both CBF (P<0.005) and MBF (P<0.05) were significantly increased by losartan in the transgenic rats. By contrast, losartan only caused a smaller decrease in MAP and an increase in renal CBF in SD rats (P<0.05). PD 123319 was without any renal effect in both SD and TGR rats. These findings suggest that markedly increased AT1 receptors in renal vasculature, glomerular mesangial cells, and RMICs in the presence of fulminant hypertension and elevated circulating and tissue Ang II levels may play an important role in the maintenance of hypertension in the Ren-2 gene transgenic rats.
Angiotensin I↗
Type 2 bradykinin-receptor antagonism does not modify kinin or angiotensin peptide levels.
Type 2 bradykinin (B2)-receptor antagonists have been used to define the role of endogenous kinin peptides. However, interpretation of the effects of B2-receptor antagonists has been limited by lack of information concerning the effects of these antagonists on endogenous kinin and angiotensin peptide levels. If kinin levels were subject to short-loop-feedback regulation mediated through B2 receptors, then a reactive increase in kinin levels might blunt the effects of B2-receptor antagonism and stimulate type 1 bradykinin receptors. Moreover, kinins have been implicated in the control of renin secretion. We investigated whether endogenous kinin levels are subject to short-loop-feedback regulation mediated by the B2 receptor and whether endogenous kinins acting through the B2 receptor influence plasma renin levels and circulating and tissue angiotensin peptide levels. The B2-receptor antagonist icatibant (1 mg/kg) was administered to rats by intraperitoneal injection, and circulating and tissue levels of angiotensin and kinin peptides were measured after 4 hours. Icatibant produced 75% occupancy of B2 receptors in the inner stripe of the renal medulla. Icatibant did not influence plasma levels of renin, angiotensinogen, angiotensin-converting enzyme, neutral endopeptidase, or circulating or tissue levels of angiotensin and bradykinin peptides. This study demonstrated that kinin levels are not subject to short-loop-feedback regulation mediated through B2 receptors and that endogenous kinin levels acting through the B2 receptor do not modulate the renin-angiotensin system.
Angiotensin II↗
Localization of angiotensin AT1 and AT2 receptors.
The distributions of angiotensin AT1 and AT2 receptors have been mapped by in vitro autoradiography throughout most tissues of many mammals, including humans. In addition to confirming that AT1 receptors occur in sites known to be targets for the physiologic actions of angiotensin, such as the adrenal cortex and medulla, renal glomeruli and proximal tubules, vascular and cardiac muscle, and brain circumventricular organs, many new sites of action have been demonstrated. In the kidney, AT1 receptors occur in high density in renal medullary interstitial cells. The function of these cells, which span the interstitial space between the tubules and the vasa rectae, remains to be determined. Renal medullary interstitial cells possess receptors for a number of vasoactive hormones in addition to AT1 receptors and this, in concert with their anatomical location, suggest that they may be important for the regulation of fluid reabsorption or renal medullary blood flow. In the heart, the highest densities of AT1 receptors occur in association with the conduction system and vagal ganglia. In the central nervous system, high AT1 receptor densities occur in many regions behind the blood-brain barrier, supporting a role for neurally derived angiotensin as a neuromodulator. The physiologic role of angiotensin in many of these brain sites remains to be determined. The AT2 receptor also has a characteristic distribution in several tissues including the adrenal gland, heart, and brain. The role of this receptor in physiology is being elucidated, but it appears to participate in development. Thus, receptor binding studies, localizing the distribution of AT1 and AT2 receptors, outline a number of regions where the actions of angiotensin are known but also provide many insights into novel physiologic roles of this peptide.
Adrenal Glands↗
Angiotensin receptors in the nervous system.
In addition to its traditional role as a circulating hormone, angiotensin is also involved in local functions through the activity of tissue renin-angiotensin systems that occur in many organs, including the brain. In the brain, both systemic and presumptive neurally derived angiotensin and angiotensin metabolites act through specific receptors to modulate many functions. This review examines the distribution of these specific angiotensin receptors and discusses evidence regarding the function of angiotensin peptides in various brain regions. Angiotensin AT1 and AT2 receptors occur in characteristic distributions that are highly correlated with the distribution of angiotensin-like immunoreactivity in nerve terminals. Acting through the AT1 receptor in the brain, angiotensin has effects on fluid and electrolyte homeostasis, neuroendocrine systems, autonomic pathways regulating cardiovascular function and behavior. Angiotensin AT1 receptors are also found in many afferent and efferent components of the peripheral autonomic nervous system. The role of the AT2 receptor in the brain is less well understood, although recent knockout studies point to an involvement with behavioral and cardiovascular functions. In addition to the AT1 and AT2 receptors, receptors for other fragments of angiotensin have been proposed. The AT4 binding site, which binds angiotensin, has a widespread distribution in the brain quite distinct from that of the AT1 and AT2 receptors. It is associated with many cholinergic neuronal groups and also several sensory nuclei, but its function remains to be determined. Our discovery that another brain-derived peptide binds to the AT4 binding site in the brain and may represent the native ligand is discussed. Overall, the distribution of angiotensin receptors in the brain indicate that they play diverse and important physiological roles in the nervous system.
Animals↗
Bioactive angiotensin peptides.
Angiotensin II is recognised as the principle active peptide of the renin-angiotensin system, exerting effects on fluid and electrolyte homeostasis, and cardiovascular control including neural and long term trophic effects. However, recent studies indicate that other angiotensin peptides such as angiotensin III, angiotensin II (1-7) and angiotensin IV, may have specific actions. Interestingly, recent work involving angiotensin IV demonstrates that this peptide binds to specific receptors and may be involved in memory retention and neuronal development. Furthermore, our demonstration that a globin fragment, LVV-haemorphin-7, binds with high affinity to the angiotensin IV binding site and is abundant in the brain, indicates that this may represent a novel brain neuropeptide system. It now appears, that the renin-angiotensin system is more complex than previously thought and capable of generating multiple, active peptides which elicit numerous diverse actions.
Angiotensin II↗
Localization and interactions of vasoactive peptide receptors in renomedullary interstitial cells of the kidney.
Vasoactive peptides regulate renal medullary microcirculation and tubular function, but the localization of their receptors and mechanisms of actions are currently unknown. Using electron microscopic autoradiography, we have mapped the receptors for angiotensin II (Ang II [AT1 and AT2]), endothelin (ET(A) and ET(B)), and bradykinin (B2) in the rat renal medulla. Although these peptide receptors show distinct vascular and tubular distributions, they overlap strikingly in renomedullary interstitial cells (RMICs) of the inner stripe and the papilla. Using reverse transcription-polymerase chain reaction (RT-PCR) and Southern analysis, mRNAs for AT1A, ET(A), and B2 receptors were detected in cultured adult RMICs. Ang II increases intracellular inositol 1,4,5-triphosphate (IP3) and [Ca2+]i and stimulates [3H]thymidine incorporation and extracellular matrix (ECM) synthesis via AT1A receptors. Endothelin and bradykinin also stimulate cell proliferation and ECM synthesis in RMICs through ET(A) and B2 receptors, respectively, but the actions of endothelin are modulated by concurrent nitric oxide production. By contrast, AT2 receptor mRNA was detected only in embryonic RMICs, in which Ang II inhibits cell proliferation through this receptor. These results suggest that multiple vasoactive peptides may interact with RMICs to exert endocrine and/or paracrine influences on renal medullary microcirculation and tubular function.
Animals↗
Mapping tissue angiotensin-converting enzyme and angiotensin AT1, AT2 and AT4 receptors.
BACKGROUND: The renin-angiotensin system (RAS) functions as both a circulating endocrine system and a tissue paracrine/autocrine system. As a circulating peptide, angiotensin II (Ang II) plays a prominent role in blood-pressure control and body fluid and electrolyte balance by acting on the AT1 receptor in the brain and peripheral tissues. As a paracrine/autocrine peptide, locally formed Ang II also plays additional roles in tissues involving the regulation of regional haemodynamics, cell growth and remodelling, and neurotransmitter release. Evidence is emerging that Ang II is not the only active peptide of the RAS, and other Ang II fragments may also have important biological activities. OBJECTIVES: To provide a morphological basis for understanding novel actions of angiotensin-converting enzyme (ACE), Ang II and related peptides in tissues, this article will review the localization of ACE and AT1, AT2 and AT4 receptors in the central nervous system, blood vessels and kidney. RESULTS AND CONCLUSION: Autoradiographic mapping of the major components of the RAS has proved a valuable strategy to reveal, or suggest, cellular sites of novel actions for Ang II and related peptides in tissues. First, colocalization of ACE and AT1 receptors in the substantia nigra, the caudate nucleus and putamen of human and rat brain, which contain the dopamine-synthesizing neurons, suggests that the central RAS may be important in modulating central dopamine release. Secondly, the distribution of AT4 receptors with a striking association with cholinergic neurons, motor and sensory nuclei in the brain reveals that Ang IV may modulate central motor and sensory activities and memory. Thirdly, the occurrence of high levels of ACE and AT1 and/or AT2 receptors in the adventitia of blood vessels suggests important paracrine roles of the vascular RAS. Finally, the identification of abundant AT1 receptor and elucidation of its roles in the renomedullary interstitial cells of the kidney may provide a new impetus to study further the role of Ang II in the regulation of renal medullary function and blood pressure. Overall, circulating and locally produced Ang II and related peptides may exert a remarkable range of actions in the brain, kidney and cardiovascular system through multiple angiotensin receptors.
Animals↗
Domain 5 binds near a highly conserved dinucleotide in the joiner linking domains 2 and 3 of a group II intron.
Photocrosslinking has identified the joiner between domains 2 and 3 [J(23)] as folding near domain 5 (D5), a highly conserved helical substructure of group II introns required for both splicing reactions. D5 RNAs labeled with the photocrosslinker 4-thiouridine (4sU) reacted with highly conserved nucleotides G588 and A589 in J(23) of various intron acceptor transcripts. These conjugates retained some ribozyme function with the lower helix of D5 crosslinked to J(23), so they represent active complexes. One partner of the gamma x gamma' tertiary interaction (A587 x U887) is also in J(23); even though gamma x gamma' is involved in step 2 of the splicing reaction, D5 has not previously been found to approach gamma x gamma'. Similar crosslinking patterns between D5 and J(23) were detected both before and after step 1 of the reaction, indicating that the lower helix of D5 is positioned similarly in both conformations of the active center. Our results suggest that the purine-rich J(23) strand is antiparallel to the D5 strand containing U32 and U33. Possibly, the interaction with J(23) helps position D5 correctly in the ribozyme active site; alternatively, J(23) itself might participate in the catalytic center.
Base Sequence↗
Ontogeny of angiotensin II receptors, types 1 and 2, in ovine mesonephros and metanephros.
By RNAse protection assay, hybridization histochemistry, and in vitro autoradiography it was shown that both mRNA and protein for AT1 and AT2 receptors were present in ovine fetal meso- and metanephroi at 40 days of gestation (term approximately 150 days). AT1 mRNA was localized to presumptive mesangial cells of glomeruli at 40-, 75-, 131-gestational-day-old fetuses and two-day-old lambs, in addition to being widely present in interstitial cells of the cortex and medulla, once these zones formed (60 days). By two days after birth the medullary AT1 distribution was confined to the inner stripe of the outer medulla. AT2 mRNA was present in peripheral interstitial/tissue of the mesonephros, and interstitial tissue surrounding developing glomeruli, but not the outermost nephrogenic mesenchyme in the metanephros from 40 to approximately 131 days (the period of active nephrogenesis). In addition, AT2 mRNA was localized to epithelial cells of the macula densa in metanephroi (40 to 131 gestational days) during, but not after completion, of nephrogenesis. These studies suggest that angiotensin II (Ang II) could have differentiating effects, via AT1 receptors, from very early in development. The unique epithelial site of AT2 expression in the macula densa raises the possibility that Ang II may play a role in the invariant positioning of the macula densa at the pole of its glomerulus, via this receptor.
Aging↗
Localization of bradykinin B2 binding sites in rat kidney following chronic ACE inhibitor treatment.
Bradykinin exerts important influences on renal hemodynamics and tubular function by acting on renal bradykinin B2 receptors. However, the precise sites and mechanisms of its actions on the kidney are not known. To help elucidate the mechanisms of renal actions of bradykinin in vivo, we have employed high resolution electron microscopic autoradiography to localize bradykinin B2 binding sites in the rat kidney following intravenous administration of a radiolabeled ligand, 125I-HPP-Hoe140 (3-4-Hydroxyphenyl-propionyl-DArg0-[Hyp3-Thi5-D-Tic 7-Oic8]-bradykinin), a derivative of the highly selective bradykinin B2 receptor antagonist, Hoe140. In non-treated rats, bradykinin B2 binding sites were localized to the cell bodies and the luminal brush border of the proximal convoluted tubules in the cortex. In the medulla (except for the outer stripe of the outer medulla), binding occurred in the distal tubules, thin limbs of the loop of Henle, collecting ducts, peritubular capillary endothelium and renomedullary interstitial cells. To exclude the possibility that the radioligand may bind to angiotensin converting enzyme, rats were pretreated with the angiotensin converting enzyme inhibitor, perindopril. In these rats, binding to the cell bodies and the luminal brush border of the proximal convoluted tubules in the cortex was completely abolished, while binding remained unaltered in the medulla. Further studies using high performance liquid chromatography revealed that while the radioligand was degraded following systemic administration in nontreated rats, the degradation was significantly reduced in the rats pretreated chronically with perindopril. These results indicate that binding detected in the proximal tubules in the normal rats is due primarily to the tubular uptake of the degraded radioligand, and that bradykinin B2 binding sites occur predominantly in the renal tubules, vascular endothelium, and renomedullary interstitial cells of the renal medulla.
Angiotensin-Converting Enzyme Inhibitors↗
Acute and chronic in vivo inhibition of angiotensin-converting enzyme by perindopril in the endothelium and adventitia of large arteries and organs of the rabbit.
Angiotensin-converting enzyme (ACE) inhibitors are widely used in treating hypertension and chronic heart failure, but their precise sites and mechanisms of the actions are not completely understood. In this study, we evaluated the acute and chronic in vivo inhibition of ACE by perindopril in both the endothelium and adventitia of large blood vessels including the aorta, carotid, and femoral arteries, heart, lung, and kidney by using in vitro autoradiography with [(125)I]351A as a ligand. After short-term (0.1, 0.3, and 1 mg/kg) or long-term oral administration (0.3 mg/kg), perindopril significantly inhibited plasma ACE (p < 0.001), the plasma angiotensin II (Ang II)/Ang I ratio (p < 0.01), and decreased mean arterial pressure (p < 0.001) in a dose-related manner. In the aorta, carotid, and femoral arteries, free ACE was inhibited to a similar extent in both the endothelium and adventitia by perindopril, in a dose-dependent manner, whereas total ACE in both layers of these vessels was unaltered. Similar short- and long-term ACE inhibition by perindopril was observed in the lung and heart, with somewhat greater inhibition of kidney and plasma ACE. Vascular and tissue ACE inhibition correlated highly with both plasma ACE and the plasma Ang II/Ang I ratio (r = 0.63-0.89; p < 0.001). Whereas the effects of perindopril on blood pressure, plasma Ang II/Ang I ratio, plasma and vascular ACE were all highly dose dependent, there were no significant differences on the degree of ACE inhibition observed between the three large blood vessels or between their adventitial and endothelial layers. These results demonstrate that perindopril readily penetrates the vascular wall after short- or long-term oral administration, and in a dose-dependent manner, potently inhibits both endothelial and advential vascular ACE to a comparable degree. Therefore ACE inhibitors may be beneficial in inhibiting both circulating Ang II and its local formation in the vascular wall.
Angiotensin I↗
Localization and functional properties of angiotensin II AT1 receptors in the kidney: focus on renomedullary interstitial cells.
The renal medulla plays an important role in maintaining body fluid and electrolyte balance and long-term blood pressure homeostasis through its unique structural and functional properties. Among several humoral, paracrine factors or autocoids, angiotensin II (Ang II) has been implicated in the regulation of renal medullary function, including the medullary/papillary microcirculation, urine concentration, and blood pressure, but the mechanisms by which Ang II exerts influences in the renal medulla are largely unknown. The purpose of this review is to summarize the cellular localization, regulation, and functional properties of Ang II AT1 receptors in the kidney, with special emphasis on type I renomedullary interstitial cells (RMICs) in the renal medulla and cultured RMICs. High densities of AT1 receptors have been localized in type I RMICs in the inner stripe of the outer medulla by high resolution light and electron microscopic autoradiography following in vitro or in vivo labelling, or in cultured RMICs. Furthermore, reverse transcription polymerase chain reaction and Southern blot analysis now confirm that AT1 receptors in cultured RMICs are exclusively of the AT1A subtype. In cultured RMICs, Ang II markedly increases intracellular inositol 1,4,5-triphosphate (IP3) concentration, and stimulates cell proliferation and extracellular matrix synthesis, and these cellular responses are exclusively mediated by AT1 receptors. Considering the co-occurrence of high levels of renin, renin substrate angiotensinogen, and Ang II in the interstitial fluid compartment, and AT1 receptors in type I RMICs of the renal medulla, the AT1 receptor-bearing RMICs may be more responsive to the locally formed interstitial Ang II than to the circulating peptide. Since RMICs also contain the receptors for other vasoactive peptides, such as endothelin (ET[A] and ET[B]), natriuretic peptides (NPR[A] and NPR[B]), and bradykinin (B2), and synthesize prostaglandins and medullipins, they may serve as an important site for functional interactions between Ang II and other vasoactive peptides in modulating renal medullary function. More studies using different experimental approaches are therefore required to explore and elucidate the functional role of renal interstitial Ang II and AT1 receptors in RMICs in the physiological control of renal medullary function and in the pathophysiology of hypertension and progressive renal diseases.
Connective Tissue Cells↗