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

The newly established rat strain TGR(mREN2)27 is a monogenetic model in hypertension research. Microinjecting the mouse Ren-2d renin gene caused it to become a stable part of the genome. The rats are characterized by fulminant hypertension, low plasma active renin, suppressed kidney renin, high plasma inactive renin, and high extrarenal transgene expression, most prominently in the adrenal cortex. Additionally, they exhibit significantly enhanced excretion of corticosteroids. Here we demonstrate that part of the plasma renin and most of the adrenal renin are transgene determined and that the adrenal renin is strongly activated. TGR(mREN2)27 adrenal cells may serve as a new tool to investigate the regulation and processing of Ren-2d-derived renin and its significance in hypertension and steroid metabolism. Adrenal renin in TGR(mREN2)27 is stimulated by 8-bromo-cAMP (8-Br-cAMP), angiotensin II (ANGII), and calcium. 8-Br-cAMP significantly stimulates active renin and prorenin release, as well as Ren-2d mRNA. Interestingly, within 60 min 8-Br-cAMP, ANGII, and calcimycin stimulate active renin, but not prorenin release. This indicates different intracellular pathways. An activated adrenal renin-angiotensin system in TGR (mREN2)27 as well as the lack of negative feedback on renin secretion by ANGII may be of pathophysiological significance in this hypertensive model.
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PMID:Increased adrenal renin in transgenic hypertensive rats, TGR(mREN2)27, and its regulation by cAMP, angiotensin II, and calcium. 845 55

Diabetes mellitus and cardiovascular disorders are both common disorders, and it could be anticipated that they coexist in many patients. Diltiazem (DZ) is widely used alone or in combination with propranolol (PROP) for the treatment of hypertension and ischemic heart disease. These drugs could interfere with carbohydrate metabolism and impair glucose tolerance. The purpose of this study was to investigate the effect of oral administration of DZ, PROP (100 and 25 mg kg-1, respectively) and their combination on fasting serum glucose and insulin levels in normal and diabetic Wistar rats. Diabetes was induced by an intraperitoneal (i.p.) injection of streptozotocin (60 mg kg-1). In normal animals, serum glucose was significantly increased after DZ, PROP and DZ/PROP treatment compared to the initial values. In diabetic rats, serum glucose was significantly increased after PROP and DZ/PROP treatments, while it was slightly increased after diltiazem treatment compared to the initial values. In normal animals, plasma cAMP is significantly decreased in all treatment groups compared to the control value, while in the plasma of diabetic rats, cAMP was significantly decreased after PROP and DZ/PROP treatments when compared to the control value. Serum potassium of normal rats decreased after the diltiazem and DZ/PROP treatments, and they tend to increase slightly after PROP treatment. Serum potassium of diabetic rats was increased significantly after PROP and DZ/PROP treatments compared to the initial values. Body weight is decreased significantly in all treatment groups in normal rats while this significant decrease was observed only after DZ/PROP treatment in diabetic rats. This investigation suggests that diltiazem alone has no worsening effects on the glycemic control in diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of diltiazem and/or propranolol on rat blood glucose levels in normal and diabetic animals. 838 58

The influence of diabetes on the function of vascular endothelium was examined with respect to the role of nitric oxide (NO) in the regulation of blood pressure (BP) in vivo, the vascular relaxation, and levels of cAMP and cGMP in the effluent of the perfused mesenteric arterial bed from streptozotocin-induced diabetic rats. An intravenous injection of 100 mg/kg N omega-nitro-L-arginine methylester (L-NAME) caused hypertension in both diabetic rats and controls. However, the degree of hypertension in the diabetic rats was significantly lower than that in the controls. Acetylcholine (ACh)-induced vasorelaxation of the perfused mesenteric arterial bed decreased in diabetic rats. At the same time, the levels of cAMP and cGMP in the effluent of the diabetic rats were also lower than in the controls. These data indicate that NO formation is involved in the regulation of BP in rats, and is decreased in diabetic rats, due to an impairment of the vascular endothelium, including the endothelium of resistance vessels.
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PMID:Changes in endothelium-dependent relaxation and levels of cyclic nucleotides in the perfused mesenteric arterial bed from streptozotocin-induced diabetic rats. 839 May 94

Both genetically determined and artificially-induced hypertension lead to cardiac hypertrophy and shift the myosin heavy chain (MHC) expression to the beta-MHC form. The cause of this change in gene expression is unknown. To contribute to the understanding of this phenomenon, we correlated the MHC expression in the left ventricle with basal, Forskolin- and isoprenaline-stimulated adenylate cyclase activity (cAMP production of membrane fractions). We used two control rat strains [Wistar-Hagemann (WH), Wistar-Kyoto (WKY)] and several rat models of hypertension: one clip-one kidney (1C-1K), desoxycorticosterone-treated rats (DOCA), rats with reduced renal mass (RRM) and spontaneously hypertensive rats (SHR). The level of hypertension correlated positively with the degree of cardiac hypertrophy (P < 0.01) and negatively (P < 0.05) with cAMP production, e.g. the higher the degree of hypertension, the lower both basal and stimulated cAMP levels. In addition we found that the lower the basal, isoprenaline- and Forskolin-stimulated cAMP production the lower was the expression of the alpha-MHC isoenzyme (P < 0.05). Thus, our data suggest that the decreased alpha-MHC expression upon hypertension-induced cardiac hypertrophy could be mediated via decreased adenylate cyclase activity and thus decreased intracellular cAMP production.
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PMID:Correlation of myosin heavy chain expression in the rat with cAMP in different models of hypertension-induced cardiac hypertrophy. 839 91

We investigated the ability of the vasodilator prostaglandins E2 (PGE2) and I2 (PGI2) to counterbalance the vasoconstrictor action of thromboxane A2 (TxA2) in the rat renal vasculature during hypertension. In vivo measurements of renal blood flow (RBF) were made in 6-wk-old anesthetized spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats pretreated with indomethacin. The stable TxA2 agonist U-46619 was injected into the renal artery, and the magnitude and the kinetic parameters of the renal response were evaluated before and after continuous intrarenal infusion of a low dose of PGE2, viprostol (PGE2 analogue), PGI2, and iloprost (PGI2 analogue). The selected dose of vasodilator PGs did not affect arterial pressure and RBF. In the control period, the TxA2 agonist reduced RBF by 30% with a 90-s half time of recovery in both strains. Infusion of vasodilator PGs in young WKY significantly blunted the maximum vasoconstrictor effect of the TxA2 agonist and facilitated the recovery from vasoconstriction. In marked contrast, infusion of the vasodilator PGs in young SHR failed to affect the magnitude of the vasoconstrictor effect of the TxA2 agonist, although the recovery from vasoconstriction was facilitated as in WKY. On the other hand, infusion of bradykinin or dibutyryladenosine 3',5'-cyclic monophosphate (dibutyryl cAMP) blunted the TxA2-induced vasoconstriction to a similar degree in both strains.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vascular interactions of prostaglandins with thromboxane in kidneys of rats developing hypertension. 839 45

The effect of long-term treatment with propafenone, metoprolol and amiodarone was studied on the activity of Na,K-adenosine triphosphatase in lymphocytes and the plasma level of cAMP in patients with ventricular arrhythmias. The investigations were carried out in 86 patients with cardiac dysrhythmias caused by coronary artery disease, hypertension, post-inflammatory and alcohol cardiomyopathy and preexcitation syndrome. Propafenone was used in treatment in 31 patients, metoprolol in 30, amiodarone in 25. The activity of of Na,K-adenosine triphosphatase in lymphocytes was estimated by the method of Heagerty et al. The plasma level of cAMP was measured radioimmunologically. Disappearance of ventricular arrhythmias after treatment was accompanied by increase in activity of of Na,K-adenosine triphosphatase and decrease in plasma level of cAMP regardless of which drug was used. Ineffective treatment did not affect both parameters.
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PMID:[The effect of treatment with propafenone, metoprolol and amiodarone on lymphocyte sodium efflux and level of cAMP in serum]. 852 94

We investigated the influence of beta-adrenergic receptor activation on the control of gap junctional conductance (gj) in the heart of cardiomyopathic hamsters (11 months old). We measured gj in isolated ventricular cell pairs using two voltage-clamp circuits. Administration of isoproterenol (10(-6) mol/L) to the bath had no effect on gj in myopathic cell pairs but increased gj by 45 +/- 3% (+/- SE) in normal hamsters. Moreover, forskolin (10(-7) mol/L), an activator of adenyl cyclase, did not change gj in myopathic cells but enhanced gj by 23 +/- 2.8% in controls. Similar results were obtained with isobutylmethylxanthine (10(-6) mol/L), a phosphodiesterase inhibitor. Dibutyryl-cAMP (10(-6) mol/L), however, increased gj of cardiomyopathic cell pairs by 58 +/- 2.1% within 2 minutes and enhanced gj in controls by 50 +/- 3.6%. The effect of dibutyryl-cAMP on gj of myopathic cells was suppressed by intracellular dialysis of an inhibitor of protein kinase A. These observations indicate that the regulation of gj by the beta-adrenergic receptor-G protein-adenyl cyclase signaling system is greatly impaired in the failing heart but the ability of cAMP to increase gj is still preserved.
Hypertension 1996 Feb
PMID:Impaired regulation of cell communication by beta-adrenergic receptor activation in the failing heart. 856 50

In the present studies we have shown that atrial natriuretic factor (peptide) receptor of ANF-R2/ANP-C type is coupled to adenylyl cyclase/cAMP signal transduction system through Gi-regulatory protein and is implicated in mediating some of the physiological responses of atrial natriuretic factor or peptide (ANP). ANF-R2/ANP-C receptor-mediated adenylyl cyclase inhibition was altered in hypertension. This alteration was tissue specific. In heart, aorta, brain and adrenal, the extent of inhibition of adenylyl cyclase by ANP was enhanced in SHR as compared to age-matched WKY, whereas in platelets, the ANP-mediated inhibition was completely attenuated. The enhanced inhibition of adenylyl cyclase by ANP was also observed in heart and aorta from DOCA-salt hypertensive rats. In addition, the augmented inhibition of adenylyl cyclase by ANP was observed in 2 weeks and older SHR but not in 3-5 days old SHR. Similarly, in DOCA-salt hypertensive rats, the enhanced inhibition of adenylyl cyclase by ANP was observed after 2 weeks of DOCA-salt treatment when the blood pressure was also enhanced, however one week older SHR but not in 3-5 days old SHR. Similarly, in DOCA-salt hypertensive rats, the enhanced inhibition of adenylyl cyclase by ANP was observed after 2 weeks of DOCA-salt treatment when the blood pressure and augmented ANP-mediated inhibition of adenylyl of DOCA-salt treatment did not result in an augmented blood pressure and augmented ANP-mediated inhibition of adenylyl cyclase, suggesting that blood pressure increase may be responsible for the enhanced responsiveness of ANP to adenylyl cyclase inhibition. However, in genetic model of hypertension, the increased inhibition of adenylyl cyclase by ANP at 2 weeks of age (when the blood pressure is normal) may be implicated in the pathogenesis of hypertension. The augmented inhibition of adenylyl cyclase in cardiovascular tissues from SHR and DOCA-salt hypertensive rats may be due to the upregulation of ANF-R2/ANP-C receptors or due to the amplification of post-receptor signalling mechanisms.
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PMID:Defective ANF-R2/ANP-C receptor-mediated signalling in hypertension. 856 33

Adrenomedullin has recently been isolated from human pheochromocytoma. We designed the present study to examine the effect of adrenomedullin on the production of the vasoconstrictive and growth-promoting peptide endothelin-1 (ET-1) after stimulation with platelet-derived growth factor (PDGF) in cultured rat glomerular mesangial cells. PDGF stimulated ET-1 production in a concentration-dependent manner. Rat adrenomedullin inhibited this stimulated ET-1 production in a concentration-dependent manner between 10(-7) and 10(-8) mol/L. Rat adrenomedullin also increased the cellular level of cAMP in a concentration-dependent manner between 10(-7) and 10(-8) mol/L. Human adrenomedullin was less effective than rat adrenomedullin with respect to inhibiting ET-1 production and increasing cAMP levels. The addition of 8-bromo-cAMP (10(-3) and 10(-4) mol/L) reduced PDGF-induced ET-1 production. Furthermore, forskolin (10(-4) and 10(-5) mol/L), an activator of adenylate cyclase, reduced PDGF-induced ET-1 production. In contrast, the basal production of ET-1 was not significantly altered by rat and human adrenomedullin. These results indicate that adrenomedullin inhibits PDGF-induced ET-1 production in cultured rat mesangial cells, probably through a cAMP-dependent process.
Hypertension 1996 Mar
PMID:Interaction of adrenomedullin and platelet-derived growth factor on rat mesangial cell production of endothelin. 861 21

Nitric oxide has a diuretic effect in vivo. We have shown that nitric oxide inhibits antidiuretic hormone-stimulated osmotic water permeability in the collecting duct; however, the mechanism by which this occurs is unknown. We hypothesized that inhibition of antidiuretic hormone-stimulated water permeability by nitric oxide in the collecting duct is the result of activation of cGMP-dependent protein kinase, which in turn decreases intracellular cAMP. To test this hypothesis, we microperfused cortical collecting ducts. Antidiuretic hormone-stimulated water permeability was 317 +/- 47 microm/s (P < .001). Addition of spermine NONOate, a nitric oxide donor, to the bath decreased water permeability to 74 +/- 38 microm/s (P < .002). In the presence of LY 83583, an inhibitor of soluble guanylate cyclase, spermine NONOate did not change water permeability. Addition of spermine NONOate increased cGMP production (P < .01). In the presence of the cGMP-dependent protein kinase inhibitor, spermine NONOate did not change water permeability. Since antidiuretic hormone increases water permeability by increasing cAMP, we hypothesized that nitric oxide inhibits water permeability by decreasing cAMP. In tubules pretreated with antidiuretic hormone, intracellular cAMP was 18.9 +/- 3.9 fmol/mm. In tubules treated with antidiuretic hormone and spermine NONOate, cAMP was 9.3 +/- 1.7 fmol/mm (P < .03). We also examined the effect of spermine NONOate on dibutyryl-cAMP-stimulated water permeability. In the presence of dibutyryl-cAMP, water permeability was 388 +/- 30 microm/s. Addition of spermine NONOate had no significant effect on water permeability. Time controls and inhibitors by themselves did not change antidiuretic hormone-stimulated water permeability. We concluded that nitric oxide decreases antidiuretic hormone-stimulated water permeability by increasing cGMP via soluble guanylate cyclase, activating cGMP-dependent protein kinase and decreasing cAMP.
Hypertension 1996 Mar
PMID:Mechanism of the nitric oxide-induced blockade of collecting duct water permeability. 861 24


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