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At least 19 recordsLinked to original sources

PubMed1983

Is the adrenal angiotensin receptor angiotensin II--or angiotensin III like?

In order to determine whether the adrenal receptor is primarily directed at angiotensin II (AII) or angiotensin III (AIII) the following in vitro experiments were performed examining aldosterone responsiveness in isolated glomerulosa cells. 1) Cells exposed to increasing doses (2.4 X 10(-10)M - 2.4 X 10(-6)M) of AII or AIII were found to be significantly more responsive to AII (AII's ED50 was 6.3 X 10(-10) M vs AIII's 4.6 X 10(-9)M P less than 0.001). 2) Octapeptide analogues (Sar1 Ala8 and Asn1 Ala8), while demonstrating different inhibitory potencies relative to each other, were equally effective in blocking AII vs AIII stimulation. 3) The heptapeptide analogues (des1 Ala8 and des1 Ile8) however, inhibited AIII stimulation preferentially (P less than 0.01). 4) The 8 alanine octapeptide analogues were better inhibitors of both AII and AIII stimulation than the 8 alanine heptapeptide analogue. 5) HPLC analysis indicated that AII and AIII were being degraded at the same rate during the incubation procedure. These results, taken together, strongly suggest that the angiotensin adrenal receptor is an AII receptor.

1-Sarcosine-8-Isoleucine Angiotensin II↗

PubMed1984

Angiotensin-induced changes in the apparent size of rat liver angiotensin receptors.

Angiotensin receptors from rat liver were labeled using four different ligands: (Sar1-(3H)Tyr4)-Angiotensin ll ((3H)SarAll); (Sar1-(3H)Tyr4-lle8)-Angiotensin ll ((3H)SarlleAll); (Sar1-(125I) Tyr4-(4'-N3) Phe8)-Angiotensin ll (IN3All); (Sar1-(125I)Tyr4-(4'N3D-Phe)8)-Angiotensin ll (IN3DPheAll). (3H)SarAll and IN3All behaved like agonists and (3H)SarlleAll and IN3DPheAll like antagonists. All four ligands labeled the same population of sites. The azido derivatives allowed covalent labeling of receptors with a high yield (about 40%). Membranes were solubilized by Triton X-100 under experimental conditions which ensured complete solubilization of the liganded receptors in a stable form (less than 40% dissociation after 20 h). The apparent size of liganded angiotensin receptors was determined by gel filtration on Ultrogel ACA-34 columns and by SDS gel electrophoresis (in the case of covalent labeling). The apparent Stokes radius of solubilized angiotensin receptors was different wether the receptor was labeled with an agonist (Stokes radius = 6.2 +/- 0.1 nm (6) after labeling with (3H)SarAll) or with an antagonist (Stokes radii of 5.5 +/- 0.1 (7), and 5.6 +/- 0.1 nm (4) after labeling with (3H)SarlleAll and IN3DPheAll respectively). After covalent labeling with IN3All angiotensin receptors were eluted as a mixture of light and heavy forms. SDS gel electrophoresis revealed only one molecular entity of Mr 64,000. It is concluded that binding of an agonist to liver angiotensin receptors triggers or stabilizes an interaction with another membrane component involved in the coupling of the receptor to its primary effector.

Angiotensin II↗

PubMed1996

Angiotensin II stimulates proliferation of primary human keratinocytes via a non-AT1, non-AT2 angiotensin receptor.

Angiotensin II is a hormone with long known cardiovascular actions. Recent studies revealed an additional role for angiotensin II in the regulation of cell proliferation. This study was performed to clarify whether skin is a target organ for these novel angiotensin actions. Radioligand binding studies identified a high-affinity angiotensin receptor on human primary keratinocytes in vitro with a Kd of 4.5 nM and a Bmax of 0.12 nM. Competition experiments with losartan and PD 123177 revealed that this receptor was not of the AT1- nor the AT2-subtype. Stimulation of human keratinocytes with angiotensin II (10(-10) to 10(-5) M) led to a dose dependent increase in 3H-thymidine incorporation, indicating that the keratinocyte receptor mediates a mitogenic effect. This effect is comparable at 10(-9) M to stimulation of keratinocytes by EGF (50ng/ml) and FGF (50ng/ml). These results demonstrate for the first time a possible physiological role for angiotensin II in human skin involving the regulation of keratinocyte proliferation.

Angiotensin II↗

PubMed2002

Adenoviral-directed expression of the type 1A angiotensin receptor promotes cardiomyocyte hypertrophy via transactivation of the epidermal growth factor receptor.

Angiotensin II (Ang II) may cause cardiac hypertrophy via type 1 Ang II receptors (AT(1)) on cardiomyocytes and through growth factors released from cardiac fibroblasts. Whereas cardiomyocyte-specific AT(1) receptor expression produces cardiac hypertrophy and remodeling in vivo, delineation of the signals that mediate growth to Ang II is challenging because the prevailing in vitro model (cultured neonatal cardiomyocytes) expresses low levels of AT(1) receptor and responds inconsistently to Ang II. In this study, when AT(1A) receptors were expressed using adenovirus in cultured neonatal cardiomyocytes, Ang II stimulated a robust hypertrophy that was not secondary to the release of cardiac fibroblast-derived factors, specifically endothelin-1. Hypertrophy was accompanied by the induction of the immediate-early response genes, c-fos and c-jun, and reexpression of atrial natriuretic peptide (ANP). Ang II-induced activation of an ANP promoter-reporter was inhibited by the dominant/negative mutants, GalphaqI and N17Ras, indicating that hypertrophic signaling by the AT(1A) receptor is via heterotrimeric G protein coupling and downstream Ras pathways. AT(1A)-mediated cardiomyocyte hypertrophy and mitogen-activated protein kinase (MAPK) activation were inhibited by the MAPK kinase inhibitor, PD98059, and the epidermal growth factor (EGF) receptor kinase antagonist, AG1478, but not by PKC inhibitor, bisindolylmaleimide-1. Moreover, Ang II-induced MAPK activation was prevented by treatment with a matrix metalloproteinase inhibitor, consistent with the tyrosine phosphorylation of the EGF receptor in response to AT(1A) receptor activation. These data unequivocally demonstrate that Ang II can directly promote cardiac myocyte growth via AT(1A) receptors expressed on these cells and reveal for the first time the important contribution of EGF receptor-transactivated MAPK signaling to this process.

Adenoviridae↗

PubMed1994

The stability of angiotensin receptors and angiotensin converting enzyme in post mortem brain.

Quantitative in vitro autoradiography was used to assess the post mortem stability of angiotensin II receptors and angiotensin converting enzyme in adult sheep brainstems. There was no significant loss of angiotensin II receptor binding in brainstems stored for up to 24 h at 23 degrees C or for 8 h at 23 degrees C followed by 64 h at 4 degrees C. There was no significant decrease in angiotensin converting enzyme binding in the same nuclei after up to 48 h at 23 degrees C or after 8 h at 23 degrees C followed by up to 64 h at 4 degrees C. Interpretation of neurochemical studies of human brain tissue obtained at autopsy requires assessment of the post mortem stability of the molecules being studied. Our results indicate that angiotensin II receptors and angiotensin converting enzyme are remarkably stable in sheep brainstems after post mortem delays in excess of those usually encountered in hospital autopsies.

Animals↗

PubMed2001

The differential effect of angiotensin II and angiotensin 1-7 on norepinephrine, epinephrine, and dopamine concentrations in rat hypothalamus: the involvement of angiotensin receptors.

Angiotensin 1-7 has been recently claimed the active member of the angiotensins' family. In the present study we compared the effect of angiotensin II and angiotensin 1-7 on the concentration of dopamine, serotonin, epinephrine, and norepinephrine and some of their metabolites in the rat hypothalamus, where the levels of angiotensins are particularly high. Intracerebroventricular injection of angiotensin II, but not angiotensin 1-7, time-dependently elevated the levels of both epinephrine (p < 0.05) and norepinephrine (p < 0.05) in the hypothalamus and both effects could be prevented by intracerebroventricular injection of either AT(1) (candesartan), AT(2) (PD123319) or AT(1-7) (A-779) receptor antagonist. Neither angiotensin II nor angiotensin 1-7 produced any changes in the level of dopamine, dihydroxyphenylacetic acid, homovanilic acid, serotonin, 5-hydroxyindoleacetic acid, or tryptophan at any time point in comparison with the control groups. However, AT(1) but not AT(2) receptor blockade, unmasked the stimulatory effect of angiotensin 1-7 on dopamine concentration in the hypothalamus. Thus, angiotensin II and its active metabolite angiotensin 1-7 regulate selectively, albeit differentially, adrenergic, noradrenergic and dopaminergic systems in the hypothalamus, the effects that involve AT(1), AT(2) and AT(1-7) angiotensin receptors.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1976

Tachyphylaxis and angiotensin receptors.

Angiotensin tachyphylaxis was studied in the isolated guinea pig ileum under isometric conditions. 2. In tachyphylactic organs, the initial phasic response to angiotensin was abolished, while the tonic component of the response became faster in its onset and in its reversal (relaxation). 3. The relaxation of non-tachyphylactic organs after angiotensin washout was significantly slower than with bradykinin, des-amino-angiotensin and hexanoyl-angiotensin. This difference did not occur in tachyphylactic organs. 4. There was no correlation between production of tachyphylaxis or rate of relaxation after washout and the partition coefficient of the four peptides in an organic:aqueous solvent system. 5. It is suggested that tachyphylaxis depends on a slowly reversible alteration of a calcium translocation step in the stimulus-response coupling.

Angiotensin II↗

PubMed1987

Corticosteroids decrease glomerular angiotensin receptors.

Angiotensin II (ANG II) receptors of glomerular mesangial cells are regulated in vivo by changes in Na balance, effects that are presumed to be secondary to changes in circulating ANG II. However, since changes in ANG II were accompanied by parallel changes in plasma aldosterone in all models tested, it is possible that aldosterone may have also participated in the modulation of glomerular ANG II receptors. To test this hypothesis, short-term aldosterone infusions within the physiological range were employed to favor actions that would be mediated through a high-affinity mineralocorticoid receptor. The glucocorticoid, dexamethasone, was also tested to determine the mineralocorticoid specificity of the response. Two infusion rates were associated with a decrease in glomerular ANG II receptor density of 33 and 45%, respectively. There were no changes in the affinity of ANG II in either tissue or in adrenal receptor density. Serum potassium and urinary Na/K ratio were lower in the aldosterone group. Spironolactone abolished the effect of aldosterone consistent with an action mediated through a specific mineralocorticoid receptor. Dexamethasone administration produced similar downregulation of glomerular ANG II receptor and was unaccompanied by a change in electrolyte balance or blood volume. These studies support the hypothesis that corticosteroids modulate glomerular ANG II receptors and validate the complexity of glomerular receptor modulation. The downregulation observed would be expected to diminish the ability of ANG II to influence glomerular hemodynamics in models such as mineralocorticoid and glucocorticoid-induced hypertension.

Adrenal Cortex Hormones↗

PubMed1992

Molecular cloning of AT1 angiotensin receptors.

Angiotensin II is the principal effector molecule of the renin-angiotensin system. Its effects are mediated by cell surface proteins termed AT receptors. On the basis of radioligand binding studies, these have been pharmacologically subdivided into two classes, termed AT1 receptors and AT2 binding sites (Chiu AT, et al, Biochem Biophys Res Commun 1989;165:196-203). AT1 receptors appear to mediate the major cardiovascular effects of angiotensin II, whereas no known physiological properties appear to be coupled to AT2 binding sites (Wong PC, et al, J Pharmacol Exp Ther 1990;255:584-592). To gain further insight into the function of AT1 receptors we have isolated rat cDNA's and genes encoding two distinct but highly similar isoforms of AT1 receptors, termed AT1a and AT1b receptors. Two cDNA's encoding the vascular AT1a receptor were isolated by an expression cloning strategy from a cDNA library prepared from vascular smooth muscle cells. The properties of the clones isolated by this approach are consistent with known pharmacological, biochemical signaling, and tissue distribution properties of AT1 receptors. Using this cDNA as a probe, a second isoform of rat AT1 receptor was isolated from a genomic library. This receptor, termed the AT1b receptor, is 95% identical in amino acid sequence and is pharmacologically indistinguishable from the AT1a receptor. However, the tissue-specific expression pattern of the AT1b gene differs significantly from that for the AT1a receptor.

Amino Acid Sequence↗

PubMed2003

Rat brain pericyte cell lines expressing beta2-adrenergic receptor, angiotensin II receptor type 1A, klotho, and CXCR4 mRNAs despite having endothelial cell markers.

Pericytes are an integral component of blood capillaries, but their involvement in a variety of conditions and diseases, including hypertension and multiple sclerosis, is poorly understood. In order to analyze the mRNA expression of markers related to hypertension and multiple sclerosis in rat brain pericytes, we have established brain capillary pericyte cell lines from temperature-sensitive SV40 large T antigen transgenic rats. The newly established clones showed similar biochemical and morphological properties to primary pericytes. The expression of endothelial cell-related markers Flt-1, Flk-1, Tie-1, and Tie-2 was evaluated by RT-PCR analysis. beta2-Adrenergic receptor (beta2-AR), angiotensin II receptor type1A (AT1A), and klotho were also evaluated as markers related to hypertension and multiple sclerosis. All of the isolated clones expressed beta2-AR, AT1A and klotho genes. They also stably expressed Flt-1 and Tie-2, while Flk-1, Tie-1 and CXCR4 were expressed only at low levels in some of the clones. The expressions of AT1 in TR-PCT1 were determined by Western blotting. Angiotensin II stimulated migration of pericytes. This effect was blocked by an AT1 antagonist. The pericyte cell lines established here are pluripotent, and should be useful for analysis of the reactivity and biological roles of pericytes.

Angiotensin II↗

PubMed2004

Influence of arginine vasopressin receptors and angiotensin receptor subtypes on the water intake and arterial blood pressure induced by vasopressin injected into the lateral septal area of the rat.

In this study we investigated the influence of d(CH2)5-Tyr(Me)-[Arg8]vasopressin (AAVP) and [adamanteanacetyl1,0-ET-d-Tyr2,Val4,aminobutyryl6,Arg8,9]-[Arg8]vasopressin (ATAVP), which are antagonists of vasopressin V1 and V2 receptors, and the effects of losartan, a selective angiotensin AT1 receptor antagonist, and CGP42112A, a selective AT2 receptor antagonist, injected into the lateral septal area (LSA) on thirst and hypertension induced by [Arg8]vasopressin (AVP). AAVP and ATAVP injected into the LSA reduced the drinking responses elicited by injecting AVP into the LSA. Both the AT1 and AT2 ligands administered into the LSA elicited a concentration-dependent decrease in the water intake induced by AVP injected into the LSA, but losartan was more effective than CGP42112A. The increase in MAP, due to injection of AVP into the LSA, was reduced by prior injection of AAVP from 18 +/- 1 to 6 +/- 1 mm Hg. Losartan injected into the LSA prior to AVP reduced the increase in MAP to 7 +/- 0.8 mm Hg. ATAVP and CGP42112A produced no changes in the pressor effect of AVP. These results suggest that the dipsogenic effects induced by injecting AVP into the LSA were mediated primarily by AT1 receptors. However, doses of losartan were more effective when combined with CGP42112A than when given alone, suggesting that the thirst induced by AVP injections into LSA may involve activation of multiple AVP and angiotensin II receptor subtypes. The pressor response of AVP was reduced by losartan and by AAVP. CGP42112A and ATAVP did not change the AVP pressor response. These results suggest that facilitator effects of AVP on water intake are mediated through the activation of V1 receptors and that the inhibitory effect requires V2 receptors. The involvement of AT1 and AT2 receptors can be postulated. Based on the present findings, we suggest that the AVP in the LSA may play a role in the control of water and arterial blood pressure balance.

Animals↗

PubMed2004

Comparison of the effects of angiotensin receptor antagonist, angiotensin converting enzyme inhibitor, and their combination on regression of left ventricular hypertrophy of diabetes type 2 patients on recent onset hemodialysis therapy.

Left ventricular hypertrophy (LVH) is frequently found at the initiation of dialysis therapy of diabetic and hypertensive patients, and is highly predictive of future cardiac morbidity and mortality. In patients with hypertension and LVH, both an angiotensin converting enzyme (ACE) inhibitor and an angiotensin type 1 receptor (AT1) antagonist regress LVH. However, it remains controversial whether dual blockade of the renin-angiotensin system will regress LVH in these patients using a combination of ACE inhibitor and AT1 antagonist. Thirty-three type II diabetic patients with end-stage renal disease who had just entered into hemodialysis therapy and were diagnosed as having LVH evaluated by echocardiography were selected from three dialysis units staffed by the faculty of Saitama Medical School, Saitama, Japan between 1999 and 2001. The study was carried out for 1 year. All patients were assigned randomly to three groups with equal number: group I, an ACE inhibitor, enalapril 10 mg daily; group II, an AT1 antagonist, losartan 100 mg daily; group III, combination of enalapril 10 mg and losartan 100 mg daily. All antihypertensive drugs were given 30 min after the cessation of dialysis therapy. LVH was evaluated by echocardiography before the start of administration of drugs, at 6 months and 12 months after the start of drug therapy. Systolic blood pressure levels less than 140 mmHg were the target for the three groups. Using repeated measures analysis of variance, applied to those with four echocardiograms, there were progressive decreases over time in left ventricular mass index, posterior wall thickness and interventricular septum thickness. There were no significant differences in regression of LVH as well as blood pressure control between enalapril and losartan groups; however, dual blockade induced an additional 28% reduction in left ventricular mass index compared with any type of monotherapy. Both ACE inhibitors and AT1 antagonists benefit the regression of LVH in diabetic patients who start dialysis therapy. Moreover, combination therapy with ACE inhibitors and AT1 antagonists would provide more beneficial effects on LVH in these patients than monotherapy.

Angiotensin Receptor Antagonists↗

PubMed1989

Angiotensin receptors and angiotensin I-converting enzyme in rat intestine.

The purpose of this study was to map the distribution of angiotensin II (ANG II) receptors and ANG I-converting enzyme (ACE) in rat intestine. ANG II binding sites were visualized by in vitro autoradiography using iodinated [Sar1, Ile8]ANG II. The distribution of ACE was mapped using an iodinated derivative of lisinopril. Male Sprague-Dawley rats were killed and the interior of the whole intestine washed with ice-cold saline. Segments of duodenum, jejunum, ileum, and colon were quickly frozen in a mixture of isopentane and dry ice. Twenty-micron frozen sections were thaw-mounted onto gelatin-coated slides, incubated with either ligand, and exposed to X-ray film. After exposure and subsequent development, the films were quantitated by computerized densitometry. ANG II receptors were most dense in the colon, followed by the ileum, duodenum, and jejunum. Within each segment of intestine, specific ANG II binding sites were localized exclusively to the muscularis. In contrast, ACE was present in both the mucosa and the muscularis. The colocalization of ANG II receptors and ACE may suggest a role for locally generated ANG II in the control of intestinal function. The luminal orientation of ACE in the mucosa of the small intestine may suggest that at this site ACE serves primarily to hydrolyze dietary peptides.

Angiotensin II↗

PubMed1997

Sequential development of angiotensin receptors and angiotensin I converting enzyme during angiogenesis in the rat subcutaneous sponge granuloma.

1. The vasoconstrictor peptide antiotensin II (AII) can stimulate angiogenesis, an important process in wound healing, tumour growth and chronic inflammation. To elucidate mechanisms underlying AII-enhanced angiogenesis, we have studied a subcutaneous sponge granuloma model in the rat by use of 133Xe clearance, morphometry and quantitative in vitro autoradiography. 2. When injected directly into the sponge, AII (1 nmol day-1) increased 133Xe clearance from, and fibrovascular growth in sponge granulomas, indicating enhanced angiogenesis 6 to 12 days after implantation. This AII-enhanced angiogenesis was inhibited by daily doses (100 nmol/sponge) of the specific but subtype non-selective AII receptor antagonist (Sar1, Ile8)AII, and by the selective non-peptide AT1 receptor antagonists losartan and DuP 532. In contrast, AII-enhanced neovascularization was not inhibited by the AT2 receptor antagonist PD123319, nor was it mimicked by the AT2 receptor agonist CGP42112A (each at 100 nmol/sponge day-1). 3. AI (1 nmol/sponge day-1), the angiotensin converting enzyme (ACE) inhibitors captopril (up to 100 micrograms/sponge day-1) and lisinopril (40 micrograms/sponge day-1), or AII receptor antagonists did not affect angiogenesis in the absence of exogenous AII. 4. [125I]-(Sar1, Ile8)AII binding sites with characteristics of AT1 receptors were localized to microvessels and to non-vascular cells within the sponge stroma from 4 days after implantation, and were at higher density than in skin throughout the study. 5. [125I]-(Sar1, Ile8)AII binding sites with characteristics of AT2 receptors were localized to non-vascular stromal cells, were of lower density and appeared later than did AT1 sites. 6. The ACE inhibitor [125I]-351A bound to sites with characteristics of ACE, 14 days after sponge implantation. [125I]-351A bound less densely to sponge stroma than to skin. 7. We propose that AII can stimulate angiogenesis, acting via AT1 receptors within the sponge granuloma. AT1 and AT2 receptors and ACE develop sequentially during microvascular maturation, and the role of the endogenous angiotensin system in angiogenesis will depend on the balanced local expression of its various components. Pharmacological modulation of this balance may provide novel therapeutic approaches in angiogenesis-dependent diseases.

1-Sarcosine-8-Isoleucine Angiotensin II↗

PubMed1996

Role of type 1 and type 2 angiotensin receptors in angiotensin II-induced cardiomyocyte hypertrophy.

We compared the ability of angiotensin II (Ang II) to induce hypertrophy of neonatal rat ventricular myocytes with that of endothelin-1. Over 72 hours, Ang II (1 mumol/L) increased the ratio of protein to DNA by less than 10%, whereas endothelin-1 (100 nmol/L) produced a 28% increase. The growth effects of either agonist occurred independently of chronotropic actions. Radioligand binding studies showed that myocytes have nearly 300-fold more receptors for endothelin-1 than Ang II, and type 1 and type 2 Ang II receptor subtypes (AT1 and AT2) are present in near equal proportions. Cotreatment with a 10-fold molar excess of AT2 antagonists (PD 123177 or CGP 42112) for 72 hours augmented the Ang II-induced increase in the protein-to-DNA ratio to levels nearly as high (23%) as those with endothelin-1 (28%). AT2 antagonists enhanced Ang II stimulation of protein synthesis, as indexed by [3H]leucine incorporation, whereas an AT1 antagonist blocked Ang II-induced incorporation. An AT2 antagonist also prevented Ang II-induced protein degradation. In conclusion, Ang II-induced myocyte growth is tempered because of low AT1 levels and an antigrowth effect of AT2. These findings have potential clinical significance in that regression of hypertension-induced cardiac hypertrophy by AT1 antagonists may be in part due to an unopposed antigrowth effect of Ang II mediated via AT2.

Angiotensin II↗

PubMed1996

Rationale, background, and design of the randomized angiotensin receptor antagonist--angiotensin-converting enzyme inhibitor study (RAAS).

The randomized angiotensin receptor antagonist--angiotensin converting enzyme (ACE)--Inhibitor Study (RAAS) was designed to test the hypothesis that the addition of an angiotensin II type 1 receptor blocking agent, losartan 50 mg/day, to an ACE-inhibitor, enalapril 10 mg twice a day (group 1), will be more effective than standard-dose enalapril 10 mg twice a day (group 2) or high-dose enalapril alone 20 mg twice a day (group 3), in blocking the activation of the renin angiotensin aldosterone system in patients with heart failure and left ventricular systolic dysfunction. The addition of an angiotensin II type 1 receptor blocking agent to an ACE inhibitor would theoretically block ACE as well as non-ACE-dependent angiotensin II formation while maintaining the potential beneficial effect of ACE inhibitor-induced bradykinin formation. One hundred twenty patients with left ventricular systolic dysfunction and moderate to severe heart failure despite treatment with an ACE inhibitor will be randomized to 1 of the 3 groups and followed for 6 weeks, with an optional long-term week extension to determine the safety and tolerability of the combination of losaratan and enalapril, its effectiveness in preventing rest and exercise-induced neurohumoral activation (plasma norepinephrine, N-terminal proatrial natriuretic factor, angiotensin II, and aldosterone), as well as quality of life and exercise performance (6-minute walk test).

Angiotensin Receptor Antagonists↗

PubMed2002

Vascular and cardiac benefits of angiotensin receptor blockers.

Angiotensin II not only is a vasoconstrictor, but it also affects cell growth and apoptosis, inflammation, fibrosis, and coagulation. Blockade of the renin-angiotensin system, either with inhibitors of the generation of angiotensin (angiotensin-converting enzyme [ACE] inhibitors) or with blockers of angiotensin receptors, reduces blood pressure and inhibits other pathophysiological actions. These other effects provide benefits in coronary heart disease, heart failure, diabetic nephropathy, and stroke beyond blood pressure reduction. These benefits were first demonstrated with ACE inhibitors. However, the mechanism of action of angiotensin receptor blockers, which block angiotensin II stimulation at the angiotensin type 1 receptor but not at the type 2 receptor, may have advantages, particularly for endothelial dysfunction and vascular remodeling, as well as cardiac and renal protection. Recent multicenter trials suggest that ACE inhibitors and angiotensin receptor blockers may reduce morbidity and mortality associated with cardiovascular and renal disease beyond blood pressure reduction. Several studies with different angiotensin receptor blockers, including comparisons with ACE inhibitors, are under way, and should provide further guidance for their clinical use.

Angiotensin Receptor Antagonists↗

PubMed2001

Comparative analysis of amphibian and mammalian angiotensin receptors.

Amphibian angiotensin receptors (xAT receptors) share many similarities with mammalian type 1 angiotensin receptors (AT(1) receptors). Both xAT and AT(1) receptors belong to the super family of seven transmembrane spanning G protein-coupled receptors and share approximately 60% amino acid homology. Highly stable secondary structure in the 5' leader sequences and the presence of the mRNA destabilizing sequence (AUUUA) in the 3' untranslated region (3'UTR) of the xAT and AT(1) receptor mRNAs suggest similar mechanisms exist for regulating gene expression. Amphibian and mammalian AT receptors bind angiotensin with equivalent affinities but show marked differences in their affinities towards mammalian AT(1) receptor subtype selective non-peptide ligands. Both xAT and AT(1) receptors couple to G proteins and to the phospholipase C (PLC) signal transduction pathway. Mammalian AT(1) receptors play a key role in maintaining blood pressure and fluid homeostasis and there is considerable evidence that xAT receptors play a similarly important role in amphibians. This review focuses on the comparison of amphibian xAT receptors with mammalian AT(1) receptors in terms of their structure, pharmacology, signaling, and function.

Adrenal Cortex↗