Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transforming growth factor-beta1 (TGF-beta1), a multifunctional cytokine with fibrogenic properties, has been implicated in the pathogenesis of the vascular and target organ complications of hypertension. TGF-beta1 may also regulate blood pressure via stimulation of endothelin-1 and/or renin secretion. Herein we explored the hypothesis that circulating levels of TGF-beta1 protein (quantified using a TGF-beta1-specific sandwich ELISA) are correlates of blood pressure levels. This hypothesis was tested in 98 stable end-stage renal disease (ESRD) patients. (The use of ESRD patients as the study cohort eliminates renal function-dependent alterations in circulating levels of TGF-beta1 protein.) In addition, in view of the previously reported correlation among TGF-beta1 DNA polymorphisms and systolic blood pressure, TGF-beta1 codon 25 genotype and alleles were identified in 71 hypertensive subjects and 57 normotensives using amplification refractory mutation system polymerase chain reaction. Our studies demonstrate for the first time that TGF-beta1 levels (209+/-13 ng/mL, mean+/-SEM) are positive correlates (Pearson correlation analysis) of mean arterial pressure (P=0.008), systolic pressure (P=0.02), and diastolic pressure (P=0. 01). We also report that a higher percentage of hypertensives (92%) compared with normotensives (86%) are homozygous for the arginine allele at codon 25. Our observations support the idea that genetically determined TGF-beta1 protein concentrations may play a role in blood pressure regulation in humans.
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PMID:TGF-beta1 DNA polymorphisms, protein levels, and blood pressure. 993 Nov 16

Exogenous endothelin-1 (ET-1) is a strong vasoconstrictor in the canine kidney and causes a decrease in renal blood flow (RBF) by stimulating the ETA receptor subtype. The aim of the present study was to investigate the role of endogenously generated ET-1 in renal hemodynamics under physiological conditions. In six conscious foxhounds, the time course of the effects of the selective ETA receptor antagonist LU-135252 (10 mg/kg iv) on mean arterial blood pressure (MAP), heart rate (HR), RBF, and glomerular filtration rate (GFR), as well as its effects on renal autoregulation, were examined. LU-135252 increased RBF by 20% (from 270 +/- 21 to 323 +/- 41 ml/min, P < 0.05) and HR from 76 +/- 5 to 97 +/- 8 beats/min (P < 0. 05), but did not alter MAP, GFR, or autoregulation of RBF and GFR. Since a number of interactions between ET-1 and the renin-angiotensin system have been reported previously, experiments were repeated during angiotensin converting enzyme (ACE) inhibition by trandolaprilat (2 mg/kg iv). When ETA receptor blockade was combined with ACE inhibition, which by itself had no effects on renal hemodynamics, marked changes were observed: MAP decreased from 91 +/- 4 to 80 +/- 5 mmHg (P < 0.05), HR increased from 85 +/- 5 to 102 +/- 11 beats/min (P < 0.05), and RBF increased from 278 +/- 23 to 412 +/- 45 ml/min (P < 0.05). Despite a pronounced decrease in renal vascular resistance over the entire pressure range investigated (40-100 mmHg), the capacity of the kidneys to autoregulate RBF was not impaired. The GFR remained completely unaffected at all pressure levels. These results demonstrate that endogenously generated ET-1 contributes significantly to renal vascular tone but does not interfere with the mechanisms of renal autoregulation. If ETA receptors are blocked, then the vasoconstrictor effects of ET-1 in the kidney are compensated for to a large extent by an augmented influence of ANG II. Thus ET-1 and ANG II appear to constitute a major interrelated vasoconstrictor system in the control of RBF.
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PMID:Contribution of endothelin to renal vascular tone and autoregulation in the conscious dog. 1007 Jan 65

Adrenomedullin (ADM) is a novel peptide secretion from vascular smooth muscle, endothelial cells and other peripheral organs. It has potent and long-lasting vasodilatatory and natriuretic properties which could participate in regulating systemic blood pressure. To examine the pathophysiological role of ADM in hypertension the plasma concentrations of ADM were measured in patients with essential hypertension, before and after effective antihypertensive therapy, and in normotensive control group. Plasma ADM concentrations were increases in patients with severe hypertension and normal in patients with mild and moderate hypertension, and were decreased after effective therapy. In all hypertensive patients plasma ADM concentrations where not correlated with blood pressure, plasma renin activity, plasma endothelin-1,2, or plasma aldosterone. These results may suggest that ADM participates in defense mechanisms acting against the high elevation blood pressure in patients with hypertension.
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PMID:[Plasma adrenomodullin concentration in patients wtih essential hypertension]. 1010 71

Recent findings suggest that the ovarian renin-angiotensin system may regulate ovarian function through the paracrine/autocrine actions of angiotensin II (Ang II). In this study, we have examined and characterized the local effects of Ang II as a luteolytic factor and its interaction with prostaglandin F2alpha (PGF2alpha) and endothelin-1 (ET-1) in the bovine corpus luteum (CL) of the mid-luteal phase, by using an in vitro microdialysis system (MDS). Ang II was detected in the MDS perfusate (4 pg/ml), and infusion of PGF2alpha (10(-6) M) for 2 h increased the Ang II release by 50-100% during the following experimental period, in addition to its stimulation of ET-1 release. Two 2-h infusions of Ang II (10(-7)-10(-5) M) separated by a 2-h interval induced a dose- and time-dependent decrease of progesterone (P4) release by 41-66%. When the luteal explants were pre-perfused with PGF2alpha (10(-6) M) for 2 h, two consecutive perfusions of Ang II (10(-6) M) at a 2-h interval rapidly reduced the P4 release (by 50%). This reduction occurred 6 h earlier than those of infusions of PGF2alpha or Ang II alone. The simultaneous infusion of either 1) Ang II (10(-6) M) with PGF2alpha (10(-6) M), 2) ET-1 (10(-7) M) with PGF2alpha, or 3) Ang II + ET-1 with PGF2alpha (10(-6) M) for 2 h also induced a rapid and pronounced (60%) decrease in P4 release. Perfusion with the Ang II antagonist blocked the P4-suppressing activity of Ang II alone or PGF2alpha + Ang II infusion. Ang II stimulated the release of ET-1 and oxytocin during infusion but inhibited them after infusion. These results show that Ang II is released in the bovine midcycle CL in vitro, and this peptide, either alone or together with PGF2alpha, can suppress the release of P4. As PGF2alpha directly stimulated Ang II release, Ang II may influence the critical period for starting the cascade of functional luteolysis in vivo and might lead to structural luteolysis with ET-1 as a major vasoconstrictor. The overall results suggest that Ang II may have an important role at luteolysis in the bovine CL.
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PMID:Angiotensin II interacts with prostaglandin F2alpha and endothelin-1 as a local luteolytic factor in the bovine corpus luteum in vitro. 1020 70

Strategically located between the circulating blood and the vascular smooth muscle, endothelial cells release numerous vasoactive substances that regulate the function of vascular smooth muscle and circulating blood cells. Important endothelium-derived vasodilators are prostacyclin, bradykinin, nitric oxide (NO) and, independent of the former, endothelium-derived hyperpolarizing factor. In particular, NO inhibits cellular growth and migration. In concert with prostacyclin, NO exerts potent antiatherogenic and thromboresistant properties by preventing platelet aggregation and cell adhesion. These effects are counterbalanced by vasoconstrictors, angiotensin II and endothelin-1, both of which exert prothrombotic and growth-promoting properties. In hypertension, elevated blood pressure transmits into cardiovascular disease by causing endothelial dysfunction. Hence, modern therapeutic strategies in human hypertension focus on preserving or restoring endothelial integrity. Calcium antagonists counteract angiotensin II and endothelin-1 at the level of vascular smooth muscle by reducing the inflow of Ca2+ and facilitating the vasodilator effects of NO. Besides inhibiting the renin-angiotensin system, angiotensin-converting enzyme inhibitors diminish the inactivation of bradykinin, leading to an augmented release of NO. Newly developed vasopeptidase inhibitors induce potent antihypertensive effects in low-, normal-, and high-renin models of hypertension, not only because of the decreased breakdown of natriuretic peptides, but also because of the inhibition of endothelin-1 generation. Furthermore, experimental studies suggest that endothelin antagonists effectively lower blood pressure and prevent target-organ damage in salt-sensitive forms of hypertension. Further clinical studies are already underway to examine whether restoring endothelial dysfunction results in a clinical benefit in hypertension.
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PMID:A rationale for treatment of endothelial dysfunction in hypertension. 1034 Aug 41

Recent advances in the molecular characterization for angiotensin II (A II) related to nitric oxide, endothelin-1, prostaglandin, and adrenomedullin are reviewed. A II, the main biological active peptide of the renin-angiotensin system, plays an important role in cardiovascular homeostasis such as regulation of blood pressure and tissue remodeling. A II produces vasoconstriction by a direct action on smooth muscle cells via AT1 receptor. This action can be due to circulating A II but also to A II produced within the tissues. Nitric oxide and adrenomedullin are potent vasorelaxant substances. These substances may play a role as local antimigration factors, and antagonize the effect of A II. Whereas endothelin-1 and thromboxane A2 are vasoconstrictor substances, and may have a role as growth factors. A II and these vasoactive substances mutually exert several biological actions in cardiovascular diseases.
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PMID:[Interaction between angiotensin II and other local vasoactive substances]. 1036 43

The renin-angiotensin system plays an important role in the pathophysiology of hypertension. We studied vascular function in the aorta of mouse Ren-2 transgenic rats (TGR(mRen2)27). Changes in isometric tension of isolated aorta of TGR(mRen2)27 and Sprague-Dawley rats (SD) were recorded in organ chambers. Contractions to angiotensin II (AII), big-endothelin and endothelin-1 (ET-1), but not KCl were decreased in TGR. Blockade of nitric oxide (NO)-synthase by L-NAME or removal of the endothelium did not alter these decreased contractions to ET-1 and AII in TGR, suggesting that receptors or signaling pathways of these two agonists are downregulated during hypertension. Contractions to norepinephrine (NE) were also lower in TGR, however blockade of NO-synthase by L-NAME or removal of the endothelium evoked similar contractions to NE in both strains, suggesting that basal release of NO reduces contractions to NE to a greater extent in transgenic than control rats. In the presence of L-NAME, acetylcholine evoked endothelium-dependent contractions (EDCF) in TGR, which were blocked by the thromboxane/prostaglandin H2 receptor antagonists SQ 30741, and partially by the thromboxane synthase inhibitor CGS 13080, suggesting that prostaglandin H2 is the mediator. Endothelium-dependent relaxation to acetylcholine was decreased in TGR, while endothelium-independent relaxations to sodium nitroprusside were similar in both strains. SQ 30741 did not improve relaxations to acetylcholine in TGR indicating that impaired relaxations to acetylcholine are due to a decreased acetylcholine-receptor mediated release of NO rather than increased release of EDCF. Thus, Ren-2 hypertension leads to marked alterations of vascular functions in the aorta. These changes could contribute to hypertension and its vascular complications in TGR(mRen2)27 rats.
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PMID:Endothelial dysfunction in the aorta of transgenic rats harboring the mouse Ren-2 gene. 1036 69

To study a generalized stress reaction as well as endothelin-1 concentrations during moderate hyperbaria and hyperbaric oxygen (HBO2), eight professional divers were exposed to air (O2 21%, AIR) and oxygen (O2 100%, HBO2) at 2.5 atm abs for 60 min in separate sessions. Plasma concentrations of epinephrine, norepinephrine, dihydroxyphenylglycol (metabolite of norepinephrine), cortisol, ADH, renin, aldosterone, pro-ANP, and endothelin-1 were analyzed before, during, and 20 min after the treatments. Endothelin-1 increased significantly (6% during HBO2 and 18% during AIR, and 30 and 34% after the treatments, respectively, P = 0.032). There was no statistically significant difference in the changes of mean norepinephrine and dihydroxyphenylglycol levels between the treatments, although both seemed to change slightly during the treatments, but not over the baseline (time effect P = 0.031 and P = 0.011, respectively). Cortisol levels decreased significantly (P = 0.001) during the treatments. No significant changes were found in other analyzed hormones. The authors concluded that a) HBO2, and hyperbaric air at 2.5 atm abs do not induce a generalized hormonal stress reaction, and b) endothelin-1 increases during HBO2 and hyperbaric air at 2.5 atm abs.
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PMID:Effect of hyperbaric conditions on plasma stress hormone levels and endothelin-1. 1037 27

Ovarian Hyperstimulation Syndrome (OHSS) is a serious disorder complicating the use of ovary-stimulating drugs in assisted reproduction programs. While its pathogenesis is not fully understood, it is believed that human chorionic gonadotropin (hCG) stimulation is vital to the development of OHSS. Further evidence suggests that the renin-angiotensin pathway, vascular endothelial growth factor, endothelin-1, and cytokines all play a role in altering ovarian capillary permeability, leading to increased interstitial fluid. OHSS can produce a myriad of symptoms and signs involving numerous body systems, up to and including hypovolemic shock and acute renal failure. As growing numbers of women opt for assisted reproduction, it becomes increasingly important for emergency physicians to be able to recognize this condition. Clinical classification into mild, moderate, severe, and critical forms of OHSS can help the physician plan appropriate investigations, admission requirements, and acute management. Two cases of OHSS, representing the spectrum of this problem, are presented along with a review of the literature.
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PMID:Ovarian hyperstimulation syndrome: imperatives for the emergency physician. 1043 59

In Poland over 40% of patients are hypertensive. Majority of them suffer from essential hypertension. Its pathogenesis despite intensive studies is unclear. Many factors are thought to be involved in the pathogenesis of essential hypertension: sodium intake, obesity with insulin resistance, renin-angiotensin system, sympathetic nervous system as well as genetic factors, low birth weight and endothelial dysfunction. At present, the role of endothelin-1 is emphasized.
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PMID:[New concepts in the pathogenesis of essential hypertension]. 1049 65


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