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

We investigated the effect of antisense oligodeoxynucleotides (AS ODN) against tyrosine hydroxylase (TH) on hypertension and sympathetic nervous system activity in spontaneously hypertensive rats (SHR). Systolic blood pressure (SBP) in SHR treated with TH AS ODN (50, 200 microg/rat, i.v.) was significantly lower than that of control SHR. Epinephrine and norepinephrine levels, TH activity, and TH protein levels in the adrenal medulla of SHR were reduced concomitant with TH AS ODN treatment-induced changes in SBP. In contrast, TH AS ODN (200 microg/rat) had no effect on SBP in Wistar-Kyoto rats (WKY), despite significantly decreased catecholamine levels, TH activity, and TH protein levels. These findings suggest that peripheral systemic injection of TH AS ODN may be effective as hypotensive therapy in SHR.
 ...
PMID:Tyrosine hydroxylase antisense gene therapy causes hypotensive effects in the spontaneously hypertensive rats. 1159 96

Rat chromosome 1 has a region containing loci that influence blood pressure. In the present study, we investigated whether these loci mediate their effect via the kidney. Taking advantage of the histocompatibility between a congenic strain (WKY.SHR-Sa, which contains the relevant chromosomal region from the spontaneously hypertensive rat) and its parental strain, the Wistar-Kyoto rat (WKY), we compared the effect of transplanting a kidney at 5 to 6 weeks of age from either congenic rats or WKY into bilaterally nephrectomized WKY. WKY.SHR-Sa animals and WKY with intact kidneys and with unilateral nephrectomy were studied as controls. Blood pressure was measured at 12, 16, 20, and 25 weeks of age. At all time points, blood pressure was significantly higher (by between 8 to 22 mm Hg, P<0.001) in 2-kidney WKY.SHR-Sa animals compared with WKY. This genotype-related difference was maintained in unilaterally nephrectomized rats. Most importantly, WKY that received transplants from WKY.SHR-Sa rats had significantly higher blood pressure (P<0.001 at all time points) compared with those that received transplants from other WKY. At any age, this difference was between 70% to 100% of the difference observed between the 1-kidney groups. There was no difference in plasma urea or creatinine between groups or evidence of chronic rejection in the cross-transplant group. The findings indicate that the major proportion of the blood pressure effect of loci on rat chromosome 1 is mediated through the kidney, and provide a rational basis for investigating genes located in the relevant chromosomal region and expressed in the kidney as likely candidates.
Hypertension 2002 Sep
PMID:Kidney specificity of rat chromosome 1 blood pressure quantitative trait locus region. 1221 69

The aim of this study was to investigate the involvement of beta 3-adrenoceptors (beta 3-AR) in hypertension. Aortic rings were isolated from 12 weeks old WKY (Wistar-Kyoto) and SHR (spontaneously hypertensive rat) rats. Rings were placed in organ baths and constricted with phenylephrine. Then, cumulative concentration-relaxation curves to the beta 3-AR agonists were constructed. In both strains, SR58611, a preferential beta 3-agonist, produced similar concentration-dependent relaxation. CGP 12177 (CGP), (a partial beta 3-AR and atypical beta-AR agonist with beta 1-/beta 2-AR antagonistic properties) produced similar relaxation in WKY (pD2 = 5.10 +/- 0.06; Emax = 54 +/- 2%; n = 6) and in SHR (pD2 = 4.98 +/- 0.02; Emax = 58 +/- 4%; n = 6). In WKY, relaxant response to CGP was not modified by nadolol (10 microM) or L-748.337 (3 microM) suggesting an atypical beta-AR activation. By contrast, in SHR, the effect of CGP was strongly decreased by 3 microM L-748.337 (Emax = 27.8 +/- 5.4%; n = 7; p < 0.05 vs CGP alone), suggesting a possible participation of beta 3-AR in CGP-induced relaxation. In order to investigate the role of endothelium in CGP-induced relaxation, experiments were performed in denuded aortic rings. In WKY, CGP-induced relaxation was not modified by endothelium removal, by contrast, this was greatly inhibited in SHR (Emax = 18.3 +/- 1.9%; n = 9; p < 0.05 vs CGP in intact aortic rings). Endothelium-independent relaxation to CGP was resistant to nadolol or L-748.337 treatment which seems to rule out the involvement of beta 1, beta 2 and beta 3-AR. Endothelium-independent relaxation to CGP was significantly reduced by SQ 22536 or MDL 12330A, non-selective adenylyl cyclase inhibitors, indicating a role of cAMP-dependent pathway in CGP response. By contrast, the relaxant effect to CGP was not modified by SQ 22536 in SHR. In conclusion, these results show that [1] functional response to beta 3-AR stimulation was not altered in hypertension [2]. CGP activated an atypical beta-AR distinct from beta 1, beta 2 and beta 3-AR, partly through cAMP-dependent pathway. Impaired atypical beta-AR relaxation to CGP in SHR could contribute to the pathogenesis of the hypertension.
 ...
PMID:[Alteration in relaxation of atypical beta-adrenergic but not beta-3 receptors in arterial hypertension in the rat]. 1236 73

1. It has been demonstrated that blood pressure variability (BPV) is increased in hypertension and related to organ damage. It will be important to lower BPV in the treatment of hypertension. The present study was designed to investigate the effect of ketanserin, a 5-HT2A receptor antagonist with a weak alpha1-adrenoceptor blocking effect, on BPV in conscious spontaneously hypertensive rats (SHR). 2. It was found that ketanserin decreased blood pressure (BP) and BPV in SHR when administered intravenously (3 mg/kg, i.v.). Ketanserin decreased BPV, but not the BP level, when administered intracerebroventricularly (50 microg/rat, i.c.v.). 3. Prazosin, an alpha1-adrenoceptor antagonist, lowered BP but did not affect BPV when given either i.v. (0.5 mg/kg) or i.c.v. (30 microg/rat). Ritanserin (0.625 mg/kg, i.v.; 40 microg/rat, i.c.v.), a 5-HT2A receptor antagonist, decreased BPV only when administered i.c.v. and did not modify the BP level. 4. Ketanserin enhanced arterial baroreflex function in SHR when given either i.v. or i.c.v. 5. The stabilizing effect of ketanserin on BP was persistent when administered intragastrically. This administration route is similar to oral administration clinically. 6. It is concluded that ketanserin is an antihypertensive agent with an effect of reducing BPV. This effect is mainly mediated by central 5-HT2A receptors and is probably attributable to the restoration of arterial baroreflex function.
 ...
PMID:Ketanserin stabilizes blood pressure in conscious spontaneously hypertensive rats. 1260 50

What is the effect of melatonin on jet lag syndrome? Jet lag desynchronizes the internal sleep-wakefulness cycle with the environmental light/dark cycle. Advance (but not delay) of light onset is known to abolish pineal N-acetyltransferase activity and urine excretion of 6-sulphatoxymelatonin. Measurements of pineal serotonin, the substrate of melatonin biosynthesis; N-acetylserotonin (NAS), the immediate melatonin precursor; and melatonin (high-performance liquid chromatography-fluorimetric method) in the animal (rat) model of jet lag revealed that prolonged delay of dark-phase onset disrupted the rhytms in comparable ways as the advance of light-phase onset. Advance of dark phase onset resulted in less severe disturbances of rhythms as compared with the advance of light phase onset. Melatonin, but not NAS, injections at the beginning of a new dark period accelerated recovery of NAS and melatonin, but not serotonin, rhythms. Spontaneously hypertensive rats were more sensitive to advance of light onset and less responsive to melatonin injections than normotensive rats. NAS and methylene blue, an inhibitor of monoamine oxidase A, attenuated light-induced disruption of NAS but not melatonin rhythms. We draw the following conclusions from our data: the beginning of the dark period may be preferable to the beginning of light period as the arrival time on eastward flights; the efficacy of melatonin in alleviating jet lag may be enhanced by administering it before, during and after rapid transition through time zones; and hypertension may exaggerate jet lag syndrome.
 ...
PMID:Melatonin and jet lag syndrome: experimental model and clinical implications. 1261

In the rat, activation of alpha2-adrenergic receptors in the anterior hypothalamic nucleus inhibits sympathetic nervous system activity. Furthermore, local release of atrial natriuretic peptide inhibits norepinephrine release in this nucleus, blocking local activation of alpha2-adrenergic receptors, and thereby contributes to NaCl-sensitive hypertension in spontaneously hypertensive rats. To further test the specificity of this mechanism, either alpha2-adrenergic receptor agonists or atrial natriuretic peptide was microinjected into anterior hypothalamic nucleus of conscious C57BL/6 mice in which the alpha2-adrenergic receptor was functionally deleted by a single point mutation (n=10 per group). In control mice, microinjection of either clonidine or guanabenz (10-3 to 10-7 mol/L) caused a rapid fall in mean arterial pressure that lasted for several minutes. In the knockout mice there was no response to the injection of either dose of either agonist. Microinjection of atrial natriuretic peptide (10-6 to 10-7 mol/L) caused a rapid increase in mean arterial pressure (8.2+/-1.3 and 6.55+/-1.2 mm Hg, respectively) in the control mice that was similar to the responses previously observed in Wistar-Kyoto rats. In contrast, the microinjections did not significantly alter mean arterial pressure in the knockout mice. These experiments demonstrate that in the anterior hypothalamic nucleus of the mouse (and probably in the rat) alpha2A-adrenergic receptors mediate both sympathoinhibitory responses to alpha2-adrenergic receptor agonists and the action of atrial natriuretic peptide.
Hypertension 2003 Mar
PMID:Alpha2A-adrenergic receptors mediate sympathoinhibitory responses to atrial natriuretic peptide in the mouse anterior hypothalamic nucleus. 1262 61

It is well-known that excessive salt intake induces elevation of blood pressure and that hypertension often coexists with insulin resistance. However, the contribution made by salt intake to the development of insulin resistance remains unclear. In this minireview, the insulin resistance seen in three salt-sensitive rat models (the high-salt-fed Sprague-Dawley rat, the Dahl salt-sensitive rat and the chronically angiotensin II (AII)-infused rat) are presented. One notable observation common to all three models was that, despite their insulin-resistance, the early insulin signaling steps leading from activation of IR and IRSs to activation of PI 3-kinase Akt were apparently enhanced. This suggests that the molecular mechanism underlying the insulin resistance related to the salt-sensitive hypertension is unique. Other factors known to cause insulin resistance--e.g., obesity--actually suppress early insulin signaling, but for insulin resistance related to high-salt intake, the impaired step must be further downstream in the insulin signaling pathway. What's more, increased oxidative stress appears to be crucially involved in both AII- and high-salt-induced insulin resistance. Additional study will be necessary to fully clarify the mechanism underlying insulin resistance induced by a high-salt diet; nonetheless, the findings presented suggest the importance of developing new therapeutic approaches--e.g., potassium supplementation and anti-oxidant administration--to the treatment of insulin resistance and hypertension.
 ...
PMID:Contribution of salt intake to insulin resistance associated with hypertension. 1277 Jun 8

The vascular response to most neurotransmitters of different vascular beds is altered under hypertensive condition. The modulatory effect of genetic pulmonary arterial hypertension on histamine responses is not known. The present study was undertaken to evaluate the modulatory effect of enzymatic degradation (via histamine N-methyl-transferase and diamine oxidase) on the vascular response of histamine, and the subtype(s) of histamine receptor present in the pulmonary artery (first branch, O.D. approximately 800 microm) of the normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) (male, 22-26 weeks old). In phenylephrine (1 microM) pre-contracted preparations, histamine and 6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl) heptanecarboxamide (HTMT, a histamine H(1) receptor agonist) elicited a concentration-dependent relaxation, with a smaller magnitude recorded in SHR. Application of 10 microM S-[4-(N,N-dimethylamino)-butyl]isothiourea (SKF 91488, a selective histamine N-methyl-transferase inhibitor), but not aminoguanidine (100 microM, a diamine oxidase inhibitor), significantly attenuated histamine-induced relaxation. Clobenpropit (1 nM, a potent histamine H(3) receptor antagonist) "antagonised" the suppressive effect of SKF 91488 and histamine-evoked relaxation was restored. Endothelial denudation reduced histamine- and abolished HTMT-elicited relaxation. Dimaprit (a histamine H(2) receptor agonist) caused an endothelium-independent, cis-N-(2-phenylcyclopentyl)azacyclotridec-1-en-2-amine (MDL 12330A, 10 microM, an adenylate cyclase inhibitor)-sensitive, concentration-dependent relaxation, with a similar magnitude in both strains of rat. Histamine-evoked relaxation was reversed into a further contraction (clobenpropit (10 nM)-sensitive) (with a greater magnitude occurred in the WKY rat) after blocking the histamine H(1) and H(2) receptors with diphenhydramine plus cimetidine (30 microM each). A similar further contraction (clobenpropit-sensitive) was observed with imetit (a histamine H(3)/H(4) receptor agonist) (> or =3 microM). Under resting tension, imetit (> or =0.3 microM) caused a clobenpropit (10 nM)- and prazosin (1 microM)-sensitive, concentration-dependent contraction, with a greater contraction in the WKY rats. Our results suggest that inhibition of histamine catabolism using SKF 91488 (histamine N-methyl-transferase inhibitor) resulted in a reduction of histamine-mediated relaxation that was due to the activation of the clobenpropit-sensitive, histamine H(3)/H(4) receptor and the release of catecholamine. In addition, activation of histamine H(1) and H(2) receptors resulted in relaxation whereas histamine H(3)/H(4) receptor activation by imetit yielded a prazosin-sensitive contraction of the pulmonary artery.
 ...
PMID:An in vitro study of histamine on the pulmonary artery of the Wistar-Kyoto and spontaneously hypertensive rats. 1278 30

It is well-known that hypertension often coexists with diabetes. Based on previous reports, it appears that insulin resistance is promoted by hypertension and that hypertension is promoted by insulin resistance. In this review, we discuss hemodynamic factors underlying insulin resistance and hypertension. In addition, the insulin resistance seen in three hypertensive rat models (the high salt-fed Sprague-Dawley rat, the Dahl salt-sensitive rat and the chronically angiotensin II-infused rat) are presented. The findings presented suggest the importance of developing new therapeutic approaches (e.g., potassium supplementation and anti-oxidant administration) to the management of insulin resistance and hypertension.
 ...
PMID:[Hemodynamic factors]. 1287 69

In traditional medicine Gossypium barbadense L. is used against hypertension. Looking for a scientific basis for this use, the blood-pressure-lowering effect of the decoction of the leaves was confirmed. Fraction II (frII) of the crude extract of G. barbadense showed a dose-dependent hypotensive effect in anaesthetized rats. In hexamethonium-treated rats, the blood-pressure-lowering effect of frII was almost abolished. A small decrease of the blood-pressure-lowering effect was followed by an increase in the blood pressure. Phentolamine antagonized the increase in blood pressure in hexamethoniumtreated rats. High doses of atropine (4 mg/rat) suppressed both depressor and heart effects. In-vitro experiments revealed that atropine did not antagonize the contraction of the ileum of the rat. Tripelennamine in a concentration of 100 microg could not influence the contraction either, whereas 300 microg did. In the guinea-pig ileum 10 microg tripelennamine did not reduce the contraction significantly. In the mechanism of action of frII, acetylcholine receptors could be involved, but not histaminergic or adrenergic receptors. Although it is still not known which compound(s) in G. barbadense is (are) the active substance(s), the results obtained may explain the use of this plant in traditional medicine in Suriname.
 ...
PMID:Medicinal plants in Suriname: hypotensive effect of Gossypium barbadense. 1502 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>