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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Role of renal kallikrein-kinin system has been studied using mutant Brown-Norway Katholiek (BN-Ka) rats, in which both high- and low-molecular weight kininogens were almost absent in plasma and kinin in urine was mainly not detectable. Mutant BN-Ka rats were very sensitive to increased salt intake, resulting in raised systemic blood pressure that is linked to reduced urinary excretion of sodium, when compared with normal BN-Kitasato (BN-Ki) rats. Consequently, sodium accumulated in erythrocytes and cerebrospinal fluid in mutant BN-Ka rats. Subcutaneous infusion of angiotensin II (20 mg/day/rat) also enhanced the concentration of sodium in erythrocytes and in cerebrospinal fluid and increased the systemic pressure by releasing aldosterone. A 4-day infusion of 0.3 M sodium solution (6 ml/kg/h) to the abdominal aorta of conscious and un-restrained mutant BN-Ka rats increased the pressor responses of the arterioles to norepinephrine and angiotensin II (i.a.) by 30- and 10-fold, respectively. Infusion of ebelactone B, (a selective inhibitor of carboxypeptidase Y-like exopeptidase, a kininase in rat urine), to normal BN-Ki rats during induction of hypertension with DOCA and salt, resulted in the reduction of the raised blood pressure, indicating that a site of action of kinins was at the luminal membrane of the renal tubule cells. Our results support the view that the role of renal kallikrein-kinin system is to excrete 'excess sodium' and a reduction in the generation of renal kinins may be a factor in the development of hypertension as a result of the sodium accumulation in the body.
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PMID:Role of the renal kallikrein-kinin system in the development of hypertension. 922 52

In genetically hypertensive rats of Lyon strain (LH), both development and maintenance of hypertension are extremely sensitive to the chronic blockade of the renin-angiotensin system. However, LH rats exhibit a low renin secretory profile as indicated by (1) low basal plasma renin concentration; (2) blunted renin responses to reductions of renal perfusion pressure and beta-adrenoceptor stimulation both in vitro (isolated perfused kidney) and in vivo (conscious rat). None of the latter abnormalities are corrected by chronic sodium deprivation or when hypertension is prevented by hydralazine or perindopril treatment. Future studies will therefore have to elucidate the 'renin paradox' in LH rats.
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PMID:Renin secretion in Lyon hypertensive rats. 924 49

Angiotensin-(1-7) [Ang-(1-7)] reportedly potentiates hypotensive responses to bradykinin. We studied whether increases in circulating bradykinin would alter responses to Ang-(1-7). In rats anesthetized with thiobutabarbital, bradykinin infusion (5 microg/kg per minute I.A.) resulted in a rapid decrease in mean arterial pressure (MAP) of about 20 mm Hg (P<.01, n=9), although MAP slowly increased by 10 mm Hg after 15 minutes. When Ang-(1-7) (20, 80, and 380 nmol per rat I.A.) was given during bradykinin infusion, it elicited hypotension at 80 and 380 nmol (deltaMAP: -15+/-2.7 and -21+/-3.3 mmHg, respectively; P<.001); this hypotension was not affected by the angiotensin type 1 antagonist L-158,809 (200 microg/kg I.A.), the angiotensin type 2 antagonist PD 123319 (10 mg/kg I.A.), saralasin, or sarthran (10 microg/kg per minute). The bradykinin type 2 receptor antagonist icatibant (30 microg per rat) eliminated the hypotensive responses to Ang-(1-7), which now increased MAP at all doses tested (P<.005). Thus in the presence of bradykinin, Ang-(1-7) induces hypotensive responses that are blocked by icatibant and unaffected by angiotensin receptor antagonists. Ang-(1-7) given to saline-infused rats elicited hypertensive responses at all doses (deltaMAP: 6.4+/-1.5, 12+/-1.6, and 16.3+/-2.7 mmHg, respectively; P<.01); these responses were abolished by L-158,809 and sarthran. In rats pretreated with saralasin, Ang-(1-7) induced hypotension at 80 and 380 nmol (deltaMAP: -7.7+/-2.3 and -9.5+/-2.7, respectively; P<.05), whereas icatibant abolished this response. Thus in the rat, Ang-(1-7) can decrease blood pressure by a mechanism involving the bradykinin type 2 receptor and participates with bradykinin in a vasodepressor pathway that may serve a counterregulatory role, modulating the vasoconstrictor effects of Ang II.
Hypertension 1997 Aug
PMID:Angiotensin-(1-7) induces bradykinin-mediated hypotensive responses in anesthetized rats. 926 Sep 83

We recently reported the isolation of the klotho gene, which in predominantly expressed in the kidney and involved in human aging phenotypes. In our previous studies, we demonstrated that the Klotho protein or its metabolites may possibly function as humoral factor(s) and protect against endothelial dysfunction because acetylcholine-mediated NO production in arteries was impaired in heterozygous klotho deficient mice (kl/+). However, the pathophysiological significance of the Klotho protein has not been clarified yet. In the present study, we examined expression of the klotho gene in the kidney of the following rat models for human diseases: (1) spontaneously hypertensive rat, (2) deoxycorticosterone acetate-salt hypertensive rat, (3) 5/6 nephrectomized rat, (4) non-insulin-dependent diabetes mellitus rat (the Otsuka Long-Evans Tokushima Fatty rat), and (5) rat with acute myocardial infarction. The expression levels of klotho mRNA in the kidney in these models were significantly lower than controls except for MI rats. This is the first report showing the expression of the klotho gene in the kidney is regulated under sustained circulatory stress such as long-term hypertension, diabetes mellitus, and chronic renal failure.
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PMID:Downregulation of the Klotho gene in the kidney under sustained circulatory stress in rats. 973 Dec 28

We tested whether FR190997, a nonpeptide B(2) agonist, prevented the development of hypertension in young spontaneously hypertensive rats (SHR), which secrete less kallikrein into the urine than do Wistar-Kyoto rats. An intra-arterial (IA) injection of FR190997 (0.3 to 30 nmol/kg) caused dose-dependent hypotension in conscious Sprague-Dawley rats. Although the maximum hypotensive potency of FR190997 equaled that of bradykinin, its action lasted approximately 10 times as long. Hoe140 (100 nmol/kg IA) significantly blocked the hypotensive response induced by FR190997 (10 nmol/kg). Atropine (100 nmol/kg IA) did not affect this response. A selective infusion of FR190997 into the renal artery induced natriuresis and diuresis in anesthetized rabbits. A continuous infusion (2 nmol. 10 mL(-1). h(-1) per rat) of FR190997 into the abdominal aorta of young SHR (6 weeks old, n=6) for 6 days significantly (P<0.05) reduced mean blood pressure to 114+/-6 (day 2) and 110+/-6 (day 5) mm Hg, from 149+/-7 and 162+/-6 mm Hg, respectively, in vehicle-infused rats (n=6). At 8 days after continuous infusion (day 14), mean blood pressure (148+/-5 mm Hg) in FR190997-infused rats remained significantly (P<0. 05) lower than that in vehicle-infused rats (190+/-6 mm Hg), almost the peak value. The mesenteric artery isolated from FR190997-treated rats (day 14) had lower contractile sensitivity to norepinephrine than that from vehicle-treated rats. These results suggested that the continuous infusion of a nonpeptide B(2) agonist may prevent hypertension if performed in the critical phase.
Hypertension 2000 Jan
PMID:A nonpeptide mimic of bradykinin blunts the development of hypertension in young spontaneously hypertensive rats. 1064 38

We analyzed the effects of a possible interaction between nitric oxide deficiency and mineralocorticoids on the long-term control of blood pressure and renal and endocrine variables. Six groups of uninephrectomized male Wistar rats were used: control animals and rats that received (1) N(G)-nitro-L-arginine methyl ester (L-NAME) subpressor (0.5 mg/100 mL drinking fluid), (2) L-NAME pressor (35 mg/100 mL drinking fluid), (3) deoxycorticosterone acetate (DOCA; 12. 5 mg/wk per rat), (4) DOCA plus L-NAME subpressor, or (5) L-NAME pressor plus DOCA. For all groups, the drinking fluid was tap water or 1% NaCl solution. We measured the time course of tail systolic blood pressure (SBP) and body weight for 3 weeks in all rats. At the end of the experimental period, we measured mean arterial pressure (direct recording) and endocrine and renal variables. Tail SBP rose significantly in the DOCA plus L-NAME subpressor-treated group but remained at normotensive levels in the DOCA-treated group. The addition of L-NAME to the subpressor dose accelerated the blood pressure increase in DOCA-salt hypertensive rats. The simultaneous administration of DOCA and L-NAME increased blood pressure and mortality rates in rats that drank water or saline compared with the rats treated with L-NAME alone. The subpressor dose of L-NAME did not increase blood pressure in saline-drinking rats. We conclude that impaired NO synthesis results in increased sensitivity to the pressor effect of mineralocorticoids in the presence or absence of an increased saline intake. Hence, nitric oxide contributes to the adaptative response to mineralocorticoid excess, perhaps through the facilitation of natriuresis and, thus, control of blood pressure.
Hypertension 2000 Mar
PMID:Interaction between nitric oxide and mineralocorticoids in the long-term control of blood pressure. 1072 May 90

Obesity and Type 2 diabetes are now major public health issues in developed nations and have reached epidemic proportions in many developing nations, as well as disadvantaged groups in developed countries, e.g., Mexican-Americans, African-Americans, and Australian Aborigines. These groups all show hyperinsulinemia and insulin resistance, which have been demonstrated to be future predictors of Type 2 diabetes and have also been suggested as key factors in the etiology of the Metabolic Syndrome. It is now increasingly recognized that Type 2 diabetes is part of a cluster of cardiovascular disease (CVD) risk factors comprising the Metabolic Syndrome. This group is at very high risk of atherosclerosis because each of the risk factors in the Metabolic Syndrome cluster in its own right is an important CVD risk factor. They also contribute cumulatively to atherosclerosis. A key strategy in reducing macrovascular disease lies in the better understanding of the Metabolic Syndrome--glucose intolerance, hypertension, hyperlipidemia, and central obesity. Although it has been suggested that hyperinsulinemia/insulin resistance is the central etiological factor for the Metabolic Syndrome, epidemiological data do not support the idea that this can account for all of the cluster abnormalities. We have animal and human data suggesting that hyperleptinemia rather than, or synergistically with, hyperinsulinemia may play a central role in the genesis of the CVD risk factor cluster that constitutes the syndrome. Studies in Psammomys obesus (the Israeli sand rat) suggest hyperinsulinemia/insulin resistance is an early metabolic lesion in the development of obesity and Type 2 diabetes. This animal also develops other features of the Metabolic Syndrome, making it an excellent model to investigate etiology. Psammomys, when placed on an ad libitum laboratory diet, develops hyperinsulinemia, insulin resistance, impaired glucose tolerance, diabetes, and dyslipidemia. It also develops hyperleptinemia and leptin insensitivity, and hyperleptinemia is correlated with insulin resistance independent of changes in body weight. It is likely that a similar sequence occurs in the transition from the prediabetic state to Type 2 diabetes in humans. More recently, other potential players in the etiology of the Metabolic Syndrome have been suggested including endothelial dysfunction and acetylation-stimulating protein (ASP). It has been suggested that endothelial dysfunction may be an antecedent for both Type 2 diabetes and the Metabolic Syndrome. In addition, ASP is a serious new candidate for an important role in insulin resistance. The ASP pathway plays a critical role in fatty acid metabolism and storage, and it has been suggested that ineffective storage of fatty acids by adipocytes due to a defect in the ASP pathway may lead to insulin resistance and Type 2 diabetes.
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PMID:Etiology of the metabolic syndrome: potential role of insulin resistance, leptin resistance, and other players. 1084 50

Moxonidine, an antihypertensive imidazoline compound, reduces blood pressure by selective activation of central imidazoline I(1)-receptors and inhibition of sympathetic nerve activity and by direct actions on the kidney, with both mechanisms resulting in diuresis and natriuresis. We hypothesized that the hypotensive and renal actions of moxonidine may be mediated by atrial natriuretic peptide (ANP), a cardiac peptide involved in pressure and volume homeostasis through its vasodilatory, diuretic, and natriuretic actions. Renal parameters were measured on an hourly basis over a period of 4 hours in conscious rats that received bolus intravenous injections of moxonidine (1 to 150 microg/300 microL saline). During the first hour, moxonidine dose-dependently stimulated diuresis, natriuresis, kaliuresis, and urinary cGMP, the index of ANP activity. Moxonidine (50 microg) significantly (P<0.001) stimulated urinary volume (0.35+/-0.04 versus 1.05+/-0.09 mL/h per 100 g), sodium (14. 3+/-2.5 versus 51.8+/-6.5 micromol/h per 100 g), potassium (10.5+/-2. 3 versus 32.3+/-3.2 micromol/h per 100 g), and cGMP (325+/-52 versus 744+/-120 pmol/h per 100 g). Pretreatment with a selective imidazoline receptor antagonist, efaroxan, dose-dependently inhibited moxonidine-stimulated renal parameters. Efaroxan (25 microg per rat) significantly inhibited moxonidine-stimulated diuretic and natriuretic effects and urinary cGMP excretion (744+/-120 versus 381+/-137 pmol/h per 100 g, P<0.02). The alpha(2)-adrenoceptor antagonist yohimbine (50 microg per rat) partially yet significantly inhibited moxonidine-stimulated diuresis and natriuresis but not cGMP excretion. Plasma ANP was dose-dependently increased by moxonidine and was inhibited by pretreatment with efaroxan (220.8+/-36.9 versus 100.3+/-31.7 pg/mL, P<0.03) but not by yohimbine. In conclusion, selective in vivo activation of imidazoline receptors by moxonidine is associated with dose-dependent diuresis, natriuresis, and kaliuresis as well as stimulated plasma ANP and urinary cGMP excretion, thus implicating ANP in the renal actions of moxonidine.
Hypertension 2000 Jun
PMID:Atrial natriuretic peptide is involved in renal actions of moxonidine. 1085 66

The induction of learned helpless (LH) behavior in rats is a widely used model of unipolar depression. Recent studies have linked depression with hypertension and insulin resistance as observed in obesity, but the propensity of these disorders to manifest depression has not been reported. In this study, the LH behavioral paradigm was exploited in a model of hypertension (Dahl rat) and of insulin resistance (Zucker rat) to determine the propensity of these models to develop depression and to examine the profile of markers for the propensity of the cardiovascular system (plasma renin activity) and of the hypothalamus-pituitary-adrenal axis (corticosterone) in the display of propensity to depression. Results show that Zucker rats displayed the lowest propensity to the development of LH behavior (12%), followed by the control Sprague-Dawley rats (27%), and then Dahl rats (66%). In contrast, congenital learned helpless (cLH) rats, a genetically bred strain for animal depression, had the highest propensity (>90%). A gender effect was observed in the Zucker and cLH rats, with females showing an increased propensity to develop LH behavior. Plasma renin activity in the Dahl and Sprague-Dawley rats after the LH stress paradigm was not significantly different from baseline. In contrast, Zucker rats, with the lowest propensity to LH behavior, demonstrated a threefold increase in plasma renin activity after stress. Congenital LH rats, with the highest propensity to LH behavior, exhibited a significantly lower increase (43%) in plasma renin activity after stress. Hyporesponsive hypothalamus-pituitary-adrenal (HPA) axis functioning correlated with propensity of LH behavior. Stress-induced corticosterone levels increased under twofold in cLH rats, whereas they increased more than sevenfold in Zucker rats. Taken together, these studies suggest that whereas genetically prone hypertensive rats have a very high propensity to depression, insulin-resistant rats have a profound resistance to depression. Moreover, a hyporesponsive HPA axis may be a marker for disorders that are comorbid with depression, whereas a hyperresponsive renin-angiotensin system may be indicative of resilience.
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PMID:Hypertension and insulin resistant models have divergent propensities to learned helpless behavior in rodents. 1091 50

Vascular endothelial growth factor (VEGF) has been shown to have potent mitotic activity specific to vascular endothelial cells and has been related to vascular permeability, angiogenesis and cell proliferation in both normal and pathological situations. The present study aimed at elucidating the spatio-temporal changes in the postnatal expression pattern of VEGF in the retinae of both normal and hypertensive rats. In situ hybridization with a riboprobe showed that in the pre-hypertensive stage (2 weeks postnatal, prior to the increase of the blood pressure of the hypertensive rat), VEGF expressed strongly in the retinal pigment epithelium (RPE) and inner nuclear layer (INL) but weakly in the ganglion cell layer and nerve fiber layer in both the normal and hypertensive rats. During the early hypertensive stage (6 weeks postnatal, initial increase of the blood pressure of the hypertensive rat), similar expression pattern was maintained but the INL of the hypertensive rat was found to have more positive cells in clusters than that of the normal rat. When a sustained high blood pressure was developed (12 weeks postnatal, sustained hypertensive stage) in the hypertensive rat, the VEGF expression was much reduced in all layers of the retina although weak expression was still observed in the RPE of the normal rat and RPE and INL of the hypertensive rat. Western blot analysis however showed that VEGF protein expression in the retina was much stronger in the hypertensive rat than in the normal rat at 2 and 6 weeks postnatal. At 12 weeks, the VEGF protein returned to a level comparable to that found in the normal rat. It is speculated that the change of the VEGF protein expression pattern during the early phase of the development of hypertension may be related to the subsequent changes in the retinal vasculature of the hypertensive rat.
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PMID:Postnatal changes of vascular endothelial growth factor (VEGF) expression in the retinae of normal and hypertensive rats. 1126 91


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