Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension in 5/6 nephrectomized (CRF) rats is partly related to increased activity of the sympathetic nervous system. We have previously shown a greater norepinephrine turnover rate in the posterior hypothalamic nuclei and locus coeruleus of CRF than control rats. Dorsal rhizotomy prevented the rise in blood pressure and the increase in NE turnover rate in the posterior hypothalamus and the locus coeruleus. The studies suggest that afferent impulses from the kidney to central integrative structures in the brain may be responsible for hypertension in CRF rats. To further evaluate the role of renal afferent nerves in the regulation of blood pressure, and whether renal afferent pathways integrate with the posterior hypothalamus, we studied the effects of an intrarenal injection of 50 microliters of 10% phenol on blood pressure and NE secretion from the posterior hypothalamus of Sprague-Dawley rats. Mean arterial pressure increased from 89 +/- 4.0 to 114 +/- 4.3 mm Hg in rats which received intrarenal injection of phenol, but it did not change in rats that received vehicle (95 +/- 4.3 and 89 +/- 3.6 mm Hg, respectively). Renal denervation totally prevented the increase in blood pressure caused by intrarenal injection of phenol. The secretion of NE from the posterior hypothalamus increased from 139 +/- 4.8 to 250 +/- 9.9 pg/ml (P < 0.01) in rats that received intrarenal phenol, but it did not change in rats which received vehicle or in those with renal denervation. In CRF rats NE secretion from the posterior hypothalamus was greater than in control and CRF rats subjected to dorsal rhizotomy. These studies show that afferent impulses from an injured kidney increase NE secretion from the posterior hypothalamus and raise blood pressure. NE secretion is higher in the posterior hypothalamus of CRF than control rats. The posterior hypothalamus appears to be an important integrative structure of the sympathetic regulation of blood pressure.
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PMID:Renal afferent impulses, the posterior hypothalamus, and hypertension in rats with chronic renal failure. 906 4

The association between hypertension and chronic renal disease is well recognized. Various factors may play a role in the pathogenesis of hypertension in chronic renal failure. Those include sodium retention and volume expansion, and increased activity of vasoconstrictors, such as the renin-angiotensin system. More recently, increased activity of the sympathetic nervous system has emerged as a leading factor in the pathogenesis of hypertension in these patients. We have used the model of 5/6 nephrectomized rats to study the role of the sympathetic nervous system in the pathogenesis of this form of hypertension. We have shown greater norepinephrine turnover rate in the posterior hypothalamic nuclei and locus coeruleus of CRF than control rats. Dorsal rhizotomy prevented the rise in blood pressure and the increase in NE turnover rate in the posterior hypothalamus and the locus coeruleus. An acute injury to the kidney produced by intrarenal injection of phenol, causes an immediate rise in blood pressure and in NE secretion from the posterior hypothalamus, that can be prevented by renal denervation. Dorsal rhizotomy prevented the development of hypertension in rats with chronic renal failure. The studies suggest that afferent impulses from the kidney to central integrative structures in the brain may be responsible for the rise in blood pressure in chronic renal failure.
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PMID:Neurogenic factors and hypertension in chronic renal failure. 937 24

Hypertension is very common in patients with chronic renal failure (CRF) and it contributes to morbidity and mortality as well as to the progression of renal disease. Several mechanisms may play a role in the pathogenesis of hypertension in CRF, but the best known are sodium retention and activation of the renin-angiotensin-aldosterone system. More recently, evidence has accumulated to support a role for increased sympathetic nervous system (SNS) activity in the genesis of hypertension associated with CRF. Our laboratory findings indicate that specific renal injuries, caused by 5/6 nephrectomy and/or phenol injection in the kidney, activate renal afferent pathways that connect with integrative structures in the brain involved in the regulation of SNS activity and blood pressure. This results in a rise in blood pressure sustained by noradrenergic mechanisms. Our laboratory has also shown that the rise in central SNS activity is mitigated by increased local expression of nitric oxide synthase (NOS)-mRNA and nitric oxide (NO) production, and by upregulation of interleukin-1beta.
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PMID:The kidney and the neurogenic control of blood pressure in renal disease. 1092 99

In the recent years genetic background of pregnancy induced hypertension (PIH) are intensively investigated. Genetically determined differences in activity of renin-angiotensin system (RAS) are of importance to hypertension susceptibility. The insertion/deletion (I/D) polymorphism of angiotensin I converting enzyme (ACE) was suggested to play an important role in the aetiology of idiopathic hypertension. We have tested if this polymorphism could be associated with PIH. ACE polymorphism was investigated in 87 pregnant women with PIH and in 110 healthy pregnant women (control group). Investigation was performed by polymerase chain reaction (PCR). We have amplified genomic DNA excteracted by phenol-chloroform method from blood leucocytes. We have detected overrepresentation of the I allele in the PIH group (47.2% and 41.4% in PIH and controls, respectively). ACE genotype frequency in control group was in agreement with expected values, according to Hardy-Weinberg law, but in the PIH group the obtained values were different from expected. This observation confirmed the possible role of I allele in aetiology of PIH, and we believe that continuation of this investigation is necessary.
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PMID:[Polymorphism of gene angiotensin converting enzyme in pregnancy induced hypertension]. 1159 44

The release of Ca(2+) from intracellular stores is a fundamental element of signaling pathways involved in regulation of vascular tone, proliferation, apoptosis, and gene expression. Studies of sea urchin eggs have led to the identification of three functionally distinct Ca(2+) signaling pathways triggered by IP3, cADPR, and NAADP. The coexistence and functional relevance of these distinct intracellular Ca(2+) release systems has only been described in a few mammalian cell types. The purpose of this study was to determine whether the IP3, cADPR, and NAADP Ca(2+) release systems coexist in smooth muscle cells (SMC) and to determine the specificity of these intracellular Ca(2+) release pathways. Microsomes were prepared from rat aortic SMC (VSMC) and were loaded with 45Ca(2+). cADPR, NAADP, and IP3 induced Ca(2+) release from VSMC microsomes in a dose-dependent fashion. Heparin blocked only IP3-mediated Ca(2+) release, whereas the ryanodine channel inhibitors 8-Br-cADPR and ruthenium red blocked only cADPR-induced Ca(2+) release. Nifedipine, an L-type Ca(2+) channel blocker, inhibited NAADP elicited Ca(2+) release, but had no effect on IP3- or cADPR-mediated Ca(2+) release. An increase in pH from 7.2 to 8.2 inhibited cADPR-mediated Ca(2+) release, but had no effect on IP3- or NAADP-induced Ca(2+) release. By RT-PCR, VSMC expressed ryanodine receptor types 1, 2, and 3. Ca(2+)-dependent binding of [3H]-ryanodine to VSMC microsomes was enhanced by the ryanodine receptor agonists 4-chloro-methyl-phenol (CMP) and caffeine, but was inhibited by ruthenium red and cADPR. We conclude that VSMC possess at least three functionally distinct pathways that promote intracellular Ca(2+) release. IP3-, cADPR-, and NAADP-induced intracellular Ca(2+) release may play a critical role in the maladaptive responses of VSMC to environmental stimuli that are characteristically associated with hypertension and/or atherogenesis.
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PMID:Differential mechanisms of Ca(2+) release from vascular smooth muscle cell microsomes. 1178 82

There is substantial evidence that angiotensin II (Ang II) enhances sympathetic nervous system (SNS) activity. We recently observed that nitric oxide and interleukin-1beta (IL-1beta) exert a tonic inhibitory action on central SNS activity. Moreover, in 2 rat models of neurogenic hypertension, one caused by intrarenal injection of phenol and the other by 5/6 nephrectomy, we observed that losartan, an Ang II type 1 receptor blocker, inhibits SNS activity and increases the abundance of IL-1beta and the neuronal isoform of nitric oxide synthase (nNOS) in the posterior hypothalamic nuclei (PH), paraventricular nuclei (PVN), and locus ceruleus (LC). This raises the possibility that the stimulatory effects of Ang II on central SNS activity may be mediated by inhibition of nNOS and IL-1beta. To test this hypothesis, we studied the effect of an intracerebroventricular (ICV) infusion of Ang II on blood pressure (BP), norepinephrine (NE) secretion from the PH, renal SNS activity (RSNA), and abundance of IL-1beta and nNOS mRNA in the PH, PVN, and LC of normal Sprague-Dawley rats. Finally, we measured the concentration of nitrite/nitrate in the dialysate collected from the PH after Ang II or vehicle. ICV infusion of Ang II (100 ng/kg body wt dissolved in 10 microL of artificial cerebrospinal fluid) raised BP, RSNA, and NE secretion from the PH compared with control rats. Ang II reduced the abundance of IL-1beta and nNOS mRNA in the PH, PVN, and LC. Pretreatment with losartan (10 microg/kg body wt dissolved in 10 microL of aCSF) given ICV 20 minutes before Ang II abolished the effects of Ang II on BP, RSNA, and NE secretion from the PH and IL-1beta and nNOS mRNA. Ang II also decreased the secretion of NO from the PH. In conclusion, these studies suggest that Ang II inhibits the expression of IL-1beta and nNOS in the brain. Because locally produced NO exerts a tonic inhibitory action on SNS activity, the decrease in NO expression caused by Ang II results in greater SNS activity.
Hypertension 2002 Feb
PMID:Downregulation of neuronal nitric oxide synthase and interleukin-1beta mediates angiotensin II-dependent stimulation of sympathetic nerve activity. 1188 1

Reactive perforating collagenosis is a perforating disorder developing in adults, usually in association with diabetes mellitus or renal failure. We present three cases diagnosed at the Royal Prince Alfred Hospital in a 5 month period. All three patients had long-standing diabetes mellitus, hypertension, hypercholesterolaemia and ischaemic heart disease. Each patient presented with generalized pruritus and a papular eruption across the trunk and limbs. More than one biopsy or multiple levels were needed before the diagnostic histological features were seen. The first patient responded to 0.5% phenol with 10% glycerine in sorbolene cream. The second patient did not respond to topical betamethasone diproprionate 0.5 mg/g cream and antihistamines (hydroxyzine 25 mg nocte) and required narrow-band ultraviolet (UV) B. The third patient, having failed to respond to topical betamethasone diproprionate 0.5 mg/g cream and wet dressings, antihistamines (hydroxyzine 25 mg tds and doxepin 50 mg nocte) and UVB required acitretin 25 mg orally per day. Because reactive perforating collagenosis responds to treatment, we believe this condition should be considered in patients with diabetes mellitus or renal failure presenting with pruritus and that biopsy of intact lesions may need multiple levels to help establish the diagnosis.
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PMID:Reactive perforating collagenosis: a condition that may be underdiagnosed. 1190 64

We have developed a new model of neurogenic hypertension in the rat, in which hypertension is caused by injecting 50 microL of 10% phenol in the lower pole of one kidney. Administration of phenol in the kidney causes an immediate and persistent rise in blood pressure (BP), norepinephrine (NE) secretion from the posterior hypothalamic nuclei (PH), and renal sympathetic nerve activity (RSNA). Because angiotensin II (Ang II) is known to stimulate central and peripheral sympathetic nervous system (SNS) activity, we have tested the hypothesis that losartan, a specific Ang II AT1 receptor antagonist, may lower BP, at least in part, by SNS inhibition. To this end, we studied the effects of losartan on BP and SNS activity following intrarenal phenol injection. Central SNS activity was measured by NE secretion from the PH using a microdialysis technique, and peripheral SNS activity was measured by direct recording of renal nerve activity. At the end of the experiments, brains were isolated and interleukin (IL)-1beta and nitric oxide synthase (NOS) mRNA gene expression was measured by RT-PCR in the PH, paraventricular nuclei (PVN), and locus ceruleus (LC). The intrarenal injection of phenol raised BP, as well as central and renal SNS activity, but reduced the abundance of IL-1beta and neuronal NOS (nNOS) mRNA in the PH, PVN, and LC. Whether injected intravenously or in the lateral ventricle, losartan caused a significant (P<0.01) and dose-dependent inhibition of the effects of phenol on BP, NE secretion from the PH, and RSNA. Losartan also caused a significant (P<0.01) and dose-dependent rise in IL-1beta and nNOS-mRNA gene expression in the PH, PVN, and LC of phenol-injected rats. In conclusion, these studies have shown that the intrarenal injection of phenol causes a rise in central and renal SNS activity and a decrease in IL-1beta and nNOS-mRNA in the PH, PVN, and LC. Losartan prevented the rise in BP and SNS activity, as well as the decrease in IL-1beta and nNOS mRNA abundance caused by phenol. These studies have demonstrated that the antihypertensive action of losartan in the phenol renal injury model is largely mediated by inhibition of central and peripheral SNS activity and suggest that activation of IL-1beta and nNOS, 2 important modulators of central SNS activity, mediates the inhibitory action of losartan on SNS activity.
Hypertension 2002 Jun
PMID:Losartan reduces central and peripheral sympathetic nerve activity in a rat model of neurogenic hypertension. 1205 49

The prenyl-phenol antibiotics ascochlorin-related compounds, are known to reduce serum cholesterol and triglyceride, suppress hypertension, and ameliorate types-I and II diabetes. However, little is known about the molecular mechanism for these physiological effects. Here we report that the ascochlorin derivative, 4-O-carboxymethyl ascochlorin (AS-6) acts as a potent activator of the nuclear hormone receptor, PPARgamma, although it does not activate the related receptors, PPARalpha, PPARdelta or RARalpha. AS-6 interacts directly with the PPARgamma molecule in vitro, and induces differentiation of the mouse preadipocyte cell line 3T3-L1. Our results suggest that AS-6 is a partial agonist for PPARgamma with a novel chemical structure.
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PMID:PPARgamma activation and adipocyte differentiation induced by AS-6, a prenyl-phenol antidiabetic antibiotic. 1206 50

Intrarenal injection of phenol in rats causes a persistent elevation in blood pressure (BP) and in norepinephrine (NE) secretion from the posterior hypothalamus (PH), and downregulation of neuronal nitric oxide synthase (nNOS) and interleukin-1beta (IL-1beta) in the PH. These studies suggest that afferent impulses from the kidney to the brain may be responsible for hypertension associated with renal injury. Downregulation of nNOS and IL-1beta, two modulators of sympathetic nervous system (SNS) activity may mediate this activation. In this study we measured the effects of intrarenal phenol injection on peripheral SNS activity by direct renal nerve recording, plasma NE, nNOS, and IL-1beta abundance in the brain. We also determined whether renal denervation or administration of clonidine prevented these effects of phenol. Acutely, the phenol injection increased both afferent and efferent renal sympathetic nerve activity, decreased urinary sodium excretion, and increased plasma NE. Three weeks after the phenol injection, BP and plasma NE remained elevated. Renal denervation and pretreatment with clonidine prevented the increase in BP and plasma NE caused by phenol. Chronic renal injury caused by phenol was associated with decreased abundance of IL-1beta and nNOS in the PH. These studies have shown that a renal injury caused by phenol injection increases BP and central as well as peripheral SNS activity, which persist long after the injury. Renal denervation and antiadrenergic drugs abolish the effects of phenol on BP and plasma NE. Because NO and IL-1beta modulate SNS activity, the stimulatory action of phenol on the SNS could be mediated by downregulation of nNOS and IL-1beta in the brain.
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PMID:Renal injury caused by intrarenal injection of phenol increases afferent and efferent renal sympathetic nerve activity. 1216 Jan 95


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