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

Dopamine, an intrarenal regulator of sodium transport, is important in the pathogenesis of hypertension. The transduction of D1-like receptors in renal proximal tubules is defective in animal models of genetic hypertension. The defect is associated with an impaired regulation of proximal tubular sodium transport and cosegregates with hypertension in rats. Moreover, mice lacking one or both D1A receptor alleles develop hypertension. Extrasynaptic D3 receptors in renal tubules and juxtaglomerular cells may also regulate renal sodium transport and renin secretion while presynaptic D3 receptors may act as autoreceptors to inhibit neural norepinephrine release. Mice lacking one or both D3 alleles have elevated systolic blood pressure and developed diastolic hypertension. Although basal urine flow, sodium excretion, and glomerular filtration rate are similar, mice homozygous to the D3 receptor have an impaired ability to excrete an acute saline load compared to heterozygous and wild type mice. These studies suggest that abnormalities in dopamine receptor genes or their regulation may lead to the development of hypertension via different pathogenetic mechanisms.
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PMID:Transgenic mice to study the role of dopamine receptors in cardiovascular function. 902 32

A stimulated brain renin-angiotensin system has been implicated in genetic hypertension. We compared the effects of an intracerebroventricular injection of angiotensin II (100 ng) on the expression of inducible transcription factors c-Fos, c-Jun, and Krox-24 in the brain of spontaneously hypertensive rats (SHR). in Wistar rats with nephrogenic hypertension induced by aortic banding, and in normotensive Wistar-Kyoto and Wistar rats immunohistochemically. Generally, the angiotensin II-induced transcription factor expression was strictly confined to four distinct forebrain areas: the subfornical organ, median preoptic area, paraventricular nucleus, and supraoptic nucleus. In SHR, the angiotensin II-induced c-Fos and c-Jun expressions were significantly enhanced compared with those in normotensive control strains as well as in secondary hypertensive Wistar rats. Krox-24 expression in the subfornical organ, median preoptic area, and paraventricular nucleus of SHR was also significantly increased compared with that in all control strains. In the supraoptic nucleus, significant differences could be discriminated between SHR and secondary hypertensive Wistar rats. Injection of isotonic saline or arginine vasopressin (100 ng) as controls did not induce any expression of c-Fos, c-Jun, or Krox-24. Our findings demonstrate an enhanced sensitivity of SHR to angiotensin II-induced transcription factor expression in distinct brain areas involved in central blood pressure and osmotic control that is independent of blood pressure.
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PMID:Increased brain transcription factor expression by angiotensin in genetic hypertension. 904 Apr 44

1. Recent evidence indicates that cardiac hypertrophy induced by pressure overload is associated with a decrease in sarcoplasmic reticulum (SR) Ca2+ -ATPase of myocytes, which may contribute to a diastolic dysfunction of the heart by causing intracellular Ca2+ overload. To elucidate whether or not this is also the case in genetic hypertension, we examined cardiac mRNA levels of SR Ca2+ ATPase in 11 week old spontaneously hypertensive rats (SHR) by northern blot analysis. 2. Furthermore, to test the effects of short-term inhibition of the renin-angiotensin system on its expression, we treated 10 week old SHR with angiotensin-converting enzyme inhibitors (alacepril and imidapril) or an AT1 receptor antagonist (SC-52458) for 7 days. 3. Though the left ventricular weight of SHR was significantly higher than that of Wistar-Kyoto (WKY) rats (277 +/- 6 vs 237 +/- 4 mg/100 g bodyweight, respectively, P < 0.05), the level of SR Ca2+ -ATPase mRNA showed no difference between SHR and WKY at this age. 4. Moreover, the aforementioned three drugs did not at all affect the SR Ca2+ -ATPase expression of SHR. 5. Thus, the expression of SR Ca2+ -ATPase was not down-regulated in the heart of 11 week old SHR, and seemed not to be mediated by angiotensin AT1 receptor at this age. Since some evidence on pressure-overloaded cardiac hypertrophy indicate that the decrease in SR Ca2+ -ATPase expression occur in prominent hypertrophy and in the failured heart, further studies on cardiac SR Ca2+ -ATPase expression in more aged SHR will be required.
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PMID:Expression of sarcoplasmic reticulum Ca2+ -ATPase mRNA in the hypertrophied heart of young spontaneously hypertensive rats. 907 67

The influence of chronic angiotensin AT1 receptor blockade by specific antibody on the development of genetic hypertension was studied in young spontaneously hypertensive rats (SHR). The immunization of 4-week-old SHR with a small part of the angiotensin AT1 receptor molecule attenuated the development of hypertension in these animals. After five subcutaneous injections of the antigen both systolic and diastolic blood pressures were significantly lower (p < 0.005) in immunized SHR compared to sham-immunized SHR. No effect on blood pressure was seen in immunized Wistar-Kyoto control rats. We conclude that renin-angiotensin system might be partially involved in the development of hypertension in young spontaneously hypertensive rats because it can be attenuated by a specific antibody raised against a part of the angiotensin AT1 receptor.
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PMID:Blockade of AT1 receptors by specific antibody attenuated hypertension development in young spontaneously hypertensive rats. 908 80

To compare hypertensive end-organ damage in two genetic forms of hypertension we assessed cardiovascular function in two rat strains of genetic hypertension: transgenic rats overexpressing the mouse Ren-2 gene [(TGR(mREN2)27]) and blood pressure matched spontaneously hypertensive rats (SHR). Despite similarly elevated blood pressure, systolic dp/dt (mmHg/s) was more impaired in transgenic rats (3099 +/- 446) than in SHR (3571 +/- 272) and normals (4342 +/- 119; P < 0.05). Left ventricular weight (mg/g body weight) increased more in the transgenic rats (40 +/- 3) than in SHR (31 +/- 2) and normals (26 +/- 2). Endothelium-dependent relaxation was significantly decreased only in the transgenic rats. This study shows significantly more cardiac and endothelial dysfunction in transgenic, hypertensive TGR (mREN2)27 than in age and blood pressure matched SHR. This supports the hypothesis that chronic activation of the renin-angiotensin system significantly contributes to hypertensive end-organ damage.
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PMID:Cardiovascular end-organ damage in Ren-2 transgenic rats compared to spontaneously hypertensive rats. 918 79

The Lyon model of genetic hypertension is made of 3 simultaneously selected strains, one hypertensive (LH) one normotensive (LN) and one with low blood pressure (LL). Since LN and LL rats exhibit the same blood pressure (BP) LH rats can be compared to 2 genetically pure and different strains of control animals. This proved to be useful for the interpretation of the data of molecular genetic studies, eg: since the renin gene was polymorphic between LH and LN but not between LH and LL rats it could be suggested that the reported linkage of renin gene polymorphism and high BP in F2 hybrids may involve another closely located gene. LH rats associate to high BP spontaneous increases in body weight, plasma cholesterol, fibrinogen and hematocrit. During the phenotyping of F1 and F2 hybrids from a LH x LN cross and of back-crosses to LH rats it was observed that all these phenotypes were recessive, except the large body weight of LH rats which was dominant and, thus, unrelated to BP. On the contrary, BP was significantly related to plasma cholesterol in both F2 and back-cross rats and, in this latter cohort, plasma cholesterol correlated also with fibrinogen and hematocrit levels. Therefore, the study of the Lyon rat may be useful not only to determine the genes involved in hypertension but also those which contribute to other cardiovascular risk factors such as elevated fibrinogen and hematocrit.
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PMID:Genetics of blood pressure and associated phenotypes in the Lyon rat. 924 39

The structure and function of small arteries of different vascular beds in spontaneously hypertensive rats (SHRs) are altered relative to Wistar-Kyoto (WKY) control rats, and these differences may be blunted under treatment with angiotensin-converting enzyme inhibitors. To determine whether this effect of angiotensin-converting enzyme inhibitors was caused by the interruption of the renin-angiotensin system, our experiments were conducted with an AT1 angiotensin-receptor antagonist to evaluate its ability to induce regression of hypertrophy of resistance arteries in SHRs. The result of treatment of SHRs with losartan, an orally active selective angiotensin AT1 receptor antagonist was examined at a low (20 mg/kg/day) and a high (60 mg/kg/day) oral dose in SHRs once blood pressure had been elevated for some time. SHRs were treated for 12 weeks with losartan. Blood pressure was significantly reduced by losartan treatment from 210 +/- 2 mm Hg in untreated SHRs to 181 +/- 1 mm Hg (low dose) and 156 +/- 4 mm Hg (high dose) (p < 0.01). Cardiac and aortic hypertrophy were dose-dependently reduced in treated SHRs. Coronary, renal, mesenteric, and femoral small arteries (luminal diameter, 200-250 microm) studied on an isometric wire myograph and pressurized mesenteric small arteries examined under isobaric conditions exhibited significant hypertrophy and inward remodeling in SHRs in comparison to WKY rats. Losartan treatment resulted in a dose-dependent reduction in the media thickness and mediato-lumen ratio in small arteries from the four vascular beds studied on the wire myograph and in pressurized mesenteric small arteries. Endothelium-dependent relaxation studied in pressurized arteries was enhanced, and acetylcholine-induced endothelium-dependent contractions studied on the wire myograph were abolished in losartan-treated SHRs relative to untreated SHRs. In WKY rats, treatment had no effect. These results demonstrate that treatment with the selective angiotensin II receptor antagonist losartan, even at doses that reduce blood pressure only moderately, induces regression of cardiovascular hypertrophy and of endothelial dysfunction in genetic hypertension in the rat.
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PMID:Effect of AT1 angiotensin-receptor blockade on structure and function of small arteries in SHR. 926 24

Blood pressure is a quantitative trait that varies along a continuum in the general population and is regulated via multiple mechanisms involving many genetic loci and environmental factors. Family studies and twin studies suggest that about 30% of blood pressure variance is attributable to genetic factors and 50% to environmental factors. Two forms of hypertension transmitted on an autosomal recessive basis have been identified: one is glucocorticoid-suppressible hyperaldosteronism (GSH) and the other is Liddle's syndrome (amiloride-suppressible hyperactivity of the epithelial sodium channel). The molecular basis for these two forms of severe hypertension has recently been elucidated. GSH is due to expression of a chimeric gene produced by fusion of the 11 beta-hydroxylase promoter with the region encoding the enzyme aldosterone-synthase. Expression of this chimeric gene occurs in the zona fasciculata of the adrenal cortex, under the control of ACTH, and can be suppressed by administration of glucocorticoids. Liddle's syndrome is due to mutations in the beta or gamma chain of the epithelial sodium channel in distal renal tubule cells. The hyperactivity of this channel caused by the mutations results in increased sodium reabsorption, which can be suppressed by administration of amiloride or triamterene. Apart from these rare genetic defects, a number of susceptibility genes can increase the risk of hypertension in a given environment. Their presence is neither necessary nor sufficient to cause hypertension. The best documented example is the angiotensinogen gene. Angiotensiongen is the substrate of renin, and the renin-angiotensinogen reaction is the first and limiting step in the pathway that leads to production of angiotensin II, a peptide with important effects on blood pressure control and the metabolism of water and sodium. Several studies have demonstrated a link between the angiotensinogen gene and familial hypertension or hypertension of pregnancy. The M235T variant of angiotensinogen is more prevalent among hypertensive than among normotensive subjects in several Caucasian and Japanese populations. The M235T variant is also associated with plasma angiotensinogen elevation, which is potentially responsible for increased production of angiotensin II. In other terms, relationships exist between the angiotensinogen genotype, the intermediate phenotype (i.e., plasma angiotensinogen elevation), and the distal phenomenon (i.e., blood pressure elevation). DNA libraries for the study of hypertension have been set up, and many informative genetic markers distributed along the genome have been identified. Using position cloning techniques, these markers could be used in the search for genetic links between arterial hypertension and a chromosomal locus.
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PMID:Molecular genetics of the renin-angiotensin-aldosterone system in human hypertension. 929 68

Angiotensin (Ang)-(1-7) is a bioactive component of the renin-angiotensin system that is formed endogenously from either Ang I or Ang II. The first actions described for Ang-(1-7) indicated that the peptide mimicked some of the effects of Ang II, including the release of prostanoids and vasopressin. However, Ang-(1-7) is devoid of vasoconstrictor, central pressor, or thirst-stimulating actions. In fact, new findings reveal depressor, vasodilator, and antihypertensive actions that may be more apparent in hypertensive animals or humans. Thus, the accumulating evidence suggests that Ang-(1-7) may oppose the actions of Ang II either directly or by stimulation of prostaglandins and nitric oxide. These observations are significant because they may explain the effective antihypertensive action of converting enzyme inhibitors in a variety of non-renin-dependent models of experimental and genetic hypertension as well as most forms of human hypertension. In this context, studies in humans and animals showed that the antihypertensive action of converting enzyme inhibitors correlated with increases in plasma levels of Ang-(1-7). In this review, we summarize our knowledge of the mechanisms accounting for the counterregulatory actions of Ang-(1-7) and elaborate on the emerging concept that Ang-(1-7) functions as an antihypertensive peptide within the cascade of the renin-angiotensin system.
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PMID:Counterregulatory actions of angiotensin-(1-7). 932 78

During the past decade, it has become evident that dopamine plays an important role in the regulation of renal function and blood pressure. Dopamine exerts its actions via a class of cell-surface receptors coupled to G-proteins that belong to the rhodopsin family. Dopamine receptors have been classified into two families based on pharmacologic and molecular cloning studies. In mammals, two D1-like receptors that have been cloned, the D1 and D5 receptors (known as D1A and D1B, respectively, in rodents), are linked to stimulation of adenylyl cyclase. Three D2-like receptors that have been cloned (D2, D3, and D4) are linked to inhibition of adenylyl cyclase and Ca2+ channels and stimulation of K+ channels. All the mammalian dopamine receptors, initially cloned from the brain, have been found to be expressed outside the central nervous system, in such sites as the adrenal gland, blood vessels, carotid body, intestines, heart, parathyroid gland, and the kidney and urinary tract. Dopamine receptor subtypes are differentially expressed along the nephron, where they regulate renal hemodynamics and electrolyte and water transport, as well as renin secretion. The ability of renal proximal tubules to produce dopamine and the presence of receptors in these tubules suggest that dopamine can act in an autocrine or paracrine fashion; this action becomes most evident during extracellular fluid volume expansion. This renal autocrine/paracrine function is lost in essential hypertension and in some animal models of genetic hypertension; disruption of the D1 or D3 receptor produces hypertension in mice. In humans with essential hypertension, renal dopamine production in response to sodium loading is often impaired and may contribute to the hypertension. The molecular basis for the dopaminergic dysfunction in hypertension is not known, but may involve an abnormal post-translational modification of the dopamine receptor.
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PMID:Renal dopamine receptors in health and hypertension. 983 70


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