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

The purpose of these studies was to compare changes in conduit and resistance artery function in deoxycorticosterone-salt hypertensive rats. We hypothesized that if there was a common mechanism producing changes in vascular function in hypertension, then there would be similar alterations in reactivity of conduit and resistance arteries. Helically cut strips of common carotid artery were prepared for measurement of isometric force generation, and segments of small mesenteric arteries were pressurized for video dimension analysis. Sensitivity of arteries to phenylephrine and acetylcholine was determined. Carotid arteries from deoxycorticosterone-salt hypertensive rats were more sensitive to phenylephrine than arteries from control rats, whereas mesenteric resistance arteries from hypertensive rats were less sensitive to phenylephrine. In carotid arteries, endothelial denudation or incubation with N psi-nitro-L-arginine increased phenylephrine sensitivity in control rats to the level seen in deoxycorticosterone-salt rats. These manipulations had no effect on phenylephrine sensitivity in arteries from deoxycorticosterone-salt rats. In mesenteric resistance arteries, endothelium denudation normalized the depressed phenylephrine sensitivity in arteries from hypertensive rats but had no effect on arteries from normotensive rats. This depressed phenylephrine sensitivity in deoxycorticosterone-salt mesenteric arteries was not reversed by incubation with Npsi-nitro-L-arginine. Acetylcholine-induced relaxation was depressed in carotid arteries from deoxycorticosterone-salt hypertensive rats, and Npsi-nitro-L-arginine blocked these relaxations. In contrast, acetylcholine relaxation in the mesenteric arteries from normotensive and hypertensive rats did not differ. N psi-nitro-L-arginine slightly but significantly attenuated acetylcholine dilation only in mesenteric resistance arteries from the hypertensive rats. We conclude that qualitatively different changes in vasoconstrictor sensitivity to phenylephrine occur in carotid arteries and mesenteric resistance arteries of deoxycorticosterone-salt hypertensive rats. The increased phenylephrine sensitivity in carotid arteries in this model of hypertension is due to the loss of endothelium-derived nitric oxide production. In contrast, the decreased phenylephrine sensitivity in mesenteric resistance arteries from deoxy-corticosterone-salt rats is due to a non-nitric oxide-mediated influence of the endothelium that is absent in arteries from normotensive rats.
Hypertension 1996 Jun
PMID:Differential contribution of endothelial function to vascular reactivity in conduit and resistance arteries from deoxycorticosterone-salt hypertensive rats. 864 31

Evidence in support of prostaglandin (PG) H2 as the endothelium-derived contracting factor released in response to acetylcholine in vessels from adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) is to a large degree indirect. Therefore, the purpose of the present study was to test the hypothesis that a prostaglandin or prostaglandins other than PGH2 may serve as the endothelium-derived contracting factor that mediates acetylcholine-induced contraction in these vessels. Acetylcholine-induced contraction of endothelium-intact aorta from 7- to 12-month-old SHR and WKY in the presence of the nitric oxide synthase inhibitor N omega-nitro-L-arginine was abolished by indomethacin and only partially decreased by the thromboxane (Tx) A2/PGH2 receptor antagonist SQ29548. Contraction induced by the TxA2/ PGH2 receptor agonist U46619 was abolished by SQ29548. These findings suggest that in endothelium-intact aorta from SHR and WKY, acetylcholine causes the release of a cyclooxygenase product other than PGH2 that induces contraction independently of TxA2/PGH2 receptor activation. To investigate which prostaglandin or prostaglandins could be responsible for the TxA2/PGH2 receptor-independent component, we challenged endothelium-denuded aorta from SHR and WKY with various prostaglandins in the presence of SQ29548. In SQ29548-treated aorta from 7- to 12-month-old rats, maximal contractions to PGF2 alpha, PGE2, and carbacyclin (a PGI2 analogue) were greater than the magnitude of acetylcholine-induced contraction. These findings suggest that PGF2 alpha, PGE2, and/or PGI2 could serve as mediators of the TxA2 receptor-independent component of the acetylcholine-induced contraction. However, in studies with SQ29548-treated aorta from 4- to 6-week-old SHR and WKY (an age at which acetylcholine-induced contraction is known to be absent), maximal contraction to PGF2 alpha and PGE2 was also greater or equivalent to that of SQ29548-treated aorta from 7- to 12-month-old rats, whereas carbacyclin induced negligible contraction. Thus, unlike PGE2 and PGF2 alpha, the age-dependent pattern of contraction induced by carbacyclin closely resembles the pattern induced by acetylcholine. We also measured the levels of PGI2 released in response to acetylcholine and found that they are sufficient to account for the TxA2 receptor-independent component of the acetylcholine-induced contraction. Thus, we propose that PGI2 released in response to acetylcholine may serve as the endothelium-derived contracting factor that elicits the TxA2/PGH2 receptor-independent and dependent components of the acetylcholine-induced contraction.
Hypertension 1996 Jul
PMID:Role of prostaglandins in acetylcholine-induced contraction of aorta from spontaneously hypertensive and Wistar-Kyoto rats. 867 66

We examined the role of nitric oxide (NO) in the inherited resistance or susceptibility to hypertension in the Sabra hypertension-prone (SBH) and hypertension-resistant (SBN) rat. Basal mean arterial blood pressure was significantly greater in SBH than in SBN rats. Phenylephrine elevated blood pressure to a similar extent in both substrains, whereas the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) had a greater pressor effect in SBN rats. The vasoconstrictor potency of phenylephrine was significantly higher in endothelium-intact aortic rings from the SBH rat, whereas the vasoconstrictor potency of L-NMMA was higher in those from the SBN substrain. Acetylcholine-induced endothelium-dependent relaxation was greater in aortic rings from SBN rats. The vasodilator potency of glyceryl trinitrate was significantly higher in aortic rings from SBH rats and was enhanced after endothelium removal. Both the activity of calcium-dependent NO synthase from aortic endothelial cells and the basal concentration of nitrite/nitrate in plasma were significantly greater in SBN than in SBH rats. In normotensive Wistar rats, basal mean arterial blood pressure, the pressor effect of L-NMMA, endothelial NO synthase activity, and plasma nitrite/ nitrate concentrations were all between the values in SBH and SBN rats. These results indicate that a decrease in NO generation plays a role in the susceptibility of SBH rats to hypertension. Furthermore, the resistance to hypertension in the SBN strain may be related to increased NO generation.
Hypertension 1996 Sep
PMID:Nitric oxide and the regulation of blood pressure in the hypertension-prone and hypertension-resistant Sabra rat. 879 18

Hypertension is the main side effect developing in patients suffering from renal anemia who are treated with recombinant human erythropoietin (rHuEPO). We investigated the effect of rHuEPO on the vascular tone of isolated rabbit aorta and carotid artery under isometric conditions. The production of prostacyclin and the vasoconstrictor prostanoids PGF2 alpha and TXB2 was investigated in arterial rings incubated with rHuEPO. Endothelial cells from human umbilical veins (HUVECs) were isolated and cultured in flasks (37 degrees C, 5% CO2). After incubation with rHuEPO, the formations of prostacyclin (as its stable metabolite 6-keto-PGF1 alpha), PGF2 alpha, PGE2, thromboxane (TX) B2 and of ET-1 were measured by radioimmunoassays. rHuEPO had no direct vasoconstrictor effect, but it enhanced noradrenalin-induced contractions. This effect was more prominent in rings with intact endothelium than in rings from which the endothelium had been mechanically removed, indicating that endothelial vasoactive factors might be involved. Relaxations to acetylcholine (ACh, 1 microM) were unaltered in the presence or absence of rHuEPO, suggesting that the endothelial NO-cGMP pathway was not impaired by rHuEPO. Incubation with rHuEPO (20 to 200 U/ml) increased the release of the vasoconstrictor mediators ET-1, PGF2 alpha and TXB2, and decreased prostacyclin formation in isolated rabbit arterial rings and in HUVECs, respectively. The cyclooxygenase inhibitor indomethacin abolished the rHuEPO-induced increase in vasoconstrictor prostanoid production. ET-1 formation by HUVECs was also increased by rHuEPO in a dose-dependent manner (maximal effect +90% by rHuEPO 200 U/ml, P < 0.05). Indomethacin and the selective ETA receptor antagonist BQ123 each partly inhibited the enhancement of vascular responsiveness to noradrenalin induced by rHuEPO in rabbit carotid artery, but simultaneous administration of rHuEPO with both antagonists completely abolished the force increment. In conclusion, these studies show that a dose-dependent shift in the balance of constrictor and relaxing prostanoids as well as an increased synthesis of ET-1 induced by rHuEPO lead to the enhanced vascular responsiveness to noradrenalin in isolated rabbit arteries. The increased vascular responsiveness to noradrenalin, which is in line with clinical observations, may contribute to the hypertensive side effect associated with rHuEPO therapy in patients with chronic renal failure.
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PMID:Recombinant human erythropoietin enhances vasoconstrictor tone via endothelin-1 and constrictor prostanoids. 888 85

L-DOPA is proposed to be a neurotransmitter and/or neuromodulator in CNS. It is released probably from neurons, which may contain L-DOPA as an end-product, and/or from some compartment other than catecholamine-containing vesicles. The L-DOPA itself produces presynaptic and postsynaptic responses. All are stereoselective and most are antagonized by competitive antagonist. In striatum, L-DOPA is neuromodulator, mother of catecholamines, not only a precursor for dopamine but also a potentiator of children for presynaptic beta-adrenoceptors to facilitate dopamine release and postsynaptic D2 receptors, and ACh release inhibitor. All may cooperate for Parkinson's disease. Meanwhile, supersensitization of increase in L-glutamate release to nanomolar levodopa was seen in Parkinson's model rats, which may relate to dyskinesia or "on-off" during chronic therapy. In lower brainstem, L-DOPA tonically activates postsynaptic depressor sites of NTS and CVLM and pressor sites of RVLM. L-DOPA is probably a neurotransmitter of primary baroreceptor afferents terminating in NTS. GABA, the inhibitory neuromodulator for baroreflex in NTS, tonically functions to inhibit, via GABAA receptors, L-DOPA release and depressor responses to levodopa. Levodopa inversely releases GABA. L-DOPAergic monosynaptic relay from NTS to CVLM and from PHN to RVLM is suggested. Tonic L-DOPAergic baroreceptor-aortic nerve-NTS-CVLM relay seems to carry baroreflex information. Disturbance of neuronal activity to release L-DOPA in NTS, loss of the activity in CVLM, enhancement of the activity with decreased decarboxylation and increase in sensitivity to levodopa in RVLM may be involved in maintenance of hypertension in SHR. This is a story of "L-DOPAergic receptors" with extremely high affinity and low density.
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PMID:Neurobiology of L-DOPAergic systems. 889 95

1. Shear stress and flow influence endothelial functions to stimulate the release of endothelium-derived relaxing factor (EDRF). However, it is not well defined how hypertension affects endothelial functions. In this study, blood pressure-related changes of endothelium-dependent relaxation (EDR) in the aorta were examined in SHRSP, WKY and F1 hybrid at developmental ages of hypertension, and hypotensively-treated SHRSP. 2. Acetylcholine-induced EDR of aortic rings was significantly enhanced in 8 week old SHRSP compared with that of age-matched WKY. 3. NG-monomethyl L-arginine (L-NMMA) (1 mmol/L), an inhibitor of nitric oxide, greatly reduced the relaxation in both strains. Indomethacin (10(-5) mol/L), a cyclo-oxygenase inhibitor, did not affect the relaxation at this age. 4. EDR was positively correlated (r = 0.81, n = 22) with blood pressure at 9 weeks of age in WKY, SHRSP and F1 hybrid. 5. A five week hypotensive treatment of SHRSP caused a significant reduction in EDR with decreasing blood pressure. 6. It was concluded that the endothelium releases more EDRF in response to increasing blood pressure to regulate vascular tone at developmental ages of hypertension.
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PMID:Blood pressure-related changes of endothelium-dependent relaxation in the aorta from SHRSP at developmental ages of hypertension. 907 28

Our goal was to determine whether environmental tobacco smoke causes endothelial dysfunction in the absence of hypercholesterolemia and whether such an effect can be prevented by supplementation with L-arginine. Environmental tobacco smoke exposure is associated with an increase in coronary artery disease events and mortality. We have previously demonstrated that environmental tobacco smoke causes endothelial dysfunction and atherosclerosis in rabbits with diet-induced hypercholesterolemia and atherosclerosis and that chronic dietary L-arginine supplementation prevents this. The effects of L-arginine supplementation (2.25% solution ad libitum) and environmental tobacco smoke (smoking chambers for 10 weeks) were examined with a 2 x 2 design in 32 rabbits fed a normal diet. Acetylcholine, calcium ionophore A23187, and nitroglycerin-induced vasorelaxation were assessed in aortic rings precontracted with phenylephrine. Endothelial L-arginine levels were measured by chromatography. Chronic L-arginine supplementation increased serum (P < .001) and endothelial (P = .003) L-arginine levels. Environmental tobacco smoke reduced endothelium-dependent acetylcholine-induced relaxation, and L-arginine blocked this adverse effect (P = .04). Environmental tobacco smoke tended to increase phenylephrine-induced contraction (P = .06). Neither environmental tobacco smoke nor L-arginine influenced A23187-induced relaxation nor endothelium-independent nitroglycerin-induced relaxation. Endothelial dysfunction secondary to environmental tobacco smoke may occur in the absence of diet-induced hypercholesterolemia and atherosclerosis. Chronic dietary supplementation with a nitric oxide donor such as L-arginine offsets the endothelial dysfunction associated with environmental tobacco smoke in normocholesterolemic rabbits, possibly through substrate loading of the nitric oxide pathway.
Hypertension 1997 May
PMID:Chronic dietary L-arginine prevents endothelial dysfunction secondary to environmental tobacco smoke in normocholesterolemic rabbits. 914 85

Increased relaxant response to acetylcholine during pregnancy is proposed to be due to an estrogen-mediated increase in nitric oxide release. We studied acetylcholine-induced pathways of relaxation in the thoracic and abdominal aortic rings from pregnant and nonpregnant Wistar-Kyoto rats and measured basal and stimulated release of nitrites in these vessels. Endothelium-dependent relaxation was significantly greater in pregnant than in nonpregnant rats. Acetylcholine provoked a concentration-dependent relaxation on thoracic and abdominal aortic rings from nonpregnant and pregnant rats. After N118-nitro-L-arginine methyl ester pretreatment, the relaxation was significantly inhibited in the two preparations of nonpregnant and pregnant rodents. The relaxation was not inhibited by indomethacin in any of the aortic segments from pregnant and nonpregnant rats. After cytochrome P450 arachidonic acid metabolism inhibitor clotrimazole, a nonsignificant decrease in the Emax to acetylcholine-induced relaxation was observed in the thoracic segments of pregnant and nonpregnant rats. On the other hand, in abdominal aorta, clotrimazole decreased maximal relaxation in rings from pregnant rats (P<.05) but did not change the acetylcholine-induced relaxation from nonpregnant rats. Our results show an increase in the acetylcholine-stimulated release of nitrites in thoracic aortic rings from pregnant rats compared with rings from nonpregnant rats, which cannot be evidenced in abdominal aortic rings. These results suggest that acetylcholine-induced vasodilation in the abdominal segment from pregnant rats is mediated only in part by nitric oxide, the remainder apparently due to an endothelium-derived vasodilator, cytochrome P450-dependent, which may be endothelium-derived hyperpolarizing factor/epoxyeicosatrienoic acid.
Hypertension 1997 Sep
PMID:Possible involvement of endothelium-derived hyperpolarizing factor in vascular responses of abdominal aorta from pregnant rats. 932 88

Resistance to the vasodilator action of insulin and its capacity to antagonize vascular alpha-adrenergic reactivity may contribute to the increased neurovascular tone and blood pressure in obese hypertensive subjects. We showed that nonesterified fatty acids (NEFAs) were elevated in obese hypertensive subjects and that raising NEFAs locally in dorsal hand veins of healthy normotensive subjects enhances alpha1adrenoceptor reactivity. Research by others suggests that insulin antagonizes alpha1-adrenoceptor tone in dorsal hand veins. Taken together with evidence that NEFAs antagonize several of the metabolic actions of insulin, these observations raise the possibility that NEFAs participate in resistance to the vascular effects of insulin and suggest that dorsal hand veins represent a good model for studying these interactions. Thus, we produced local hyperinsulinemia in the dorsal hand veins of six lean normal volunteers and quantified changes of venous distensibility in response to phenylephrine in the presence and absence of a local elevation of NEFAs. We confirmed that raising NEFAs locally decreased by twofold to threefold the phenylephrine ED50 (P<.01), but this alpha1-sensitizing action of NEFAs was not antagonized by insulin concentrations up to approximately 1000 microU/mL. Moreover, local hyperinsulinemia alone did not affect vascular alpha1-adrenergic sensitivity as measured by the phenylephrine ED50. To address the possibility that the absence of an insulin effect reflected a lack of nitric oxide-mediated, endothelium-dependent dilation in hand veins, responses to acetylcholine were obtained. Acetylcholine relaxed preconstricted hand veins by 60% to 80% (P<.01) in the presence and absence of indomethacin, which suggests substantial endothelium-dependent, cyclooxygenase-independent vasodilation. The results confirm that raising NEFAs locally enhances vascular alpha1-adrenoceptor sensitivity. Despite the presence of significant endothelium-dependent dilation in dorsal hand veins, insulin does not antagonize vascular alpha1-adrenoceptor sensitivity in the presence of either ambient or locally elevated fatty acids.
Hypertension 1997 Nov
PMID:Fatty acids, not insulin, modulate alpha1-adrenergic reactivity in dorsal hand veins. 936 69

Whether nitric oxide (NO) contributes to the regulation of the mechanical properties of large arteries in humans is not known. We measured the effect of local administration of the inhibitor of NO synthesis N(G)-monomethyl-L-arginine (L-NMMA; 1 and 4 micromol x L[-1] x min[-1] for 5 minutes) and acetylcholine (3 and 30 nmol x L[-1] x min[-1] for 3 minutes) on radial artery diameter and wall thickness in 11 healthy volunteers using an echo-tracking system coupled to a measurement of radial blood flow (Doppler) and arterial pressure. At the highest dose, L-NMMA reduced radial blood flow but surprisingly decreased incremental elastic modulus (from 1.36+/-0.22 to 1.00+/-0.22 kPa x 10[3]; P<.05) and increased arterial compliance (from 3.20+/-0.46 to 4.07+/-0.45 m2 x kPa x 10(-8), P<.05), without affecting radial artery internal diameter, wall thickness or midwall stress, thus reflecting a decrease in vascular tone. Acetylcholine decreased incremental elastic modulus (from 1.27+/-0.08 to 0.88+/-0.07 kPa x 10[3]; P<.05) and increased arterial diameter, radial blood flow, and compliance (from 2.82+/-0.16 to 5.30+/-0.62m2 x kPa x 10[-8]; P<.05). These results demonstrate in vivo that NO is involved in the regulation of the mechanical properties of large arteries in humans. However, the effects of L-NMMA, ie, a decrease in arterial wall rigidity and an increase in arterial compliance, which occur in the absence of any changes in blood pressure or arterial geometry, suggest that inhibition of NO synthesis is associated in humans with a paradoxical isometric smooth muscle relaxation. This effect could be due to the development of compensatory vasodilating mechanisms after NO synthesis inhibition.
Hypertension 1997 Dec
PMID:Role of nitric oxide in the regulation of the mechanical properties of peripheral conduit arteries in humans. 940 68


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