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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension is a risk factor for coronary atherosclerosis possibly via an adverse effect on the vascular endothelium. Endothelium-mediated relaxation is impaired in animal models of hypertension. However, the effects of hypertension on human coronary artery endothelial cell function are unknown. To test whether endothelium-mediated relaxation is impaired in the coronary arteries of patients with hypertension, we studied 14 patients with essential hypertension requiring therapy and 15 nonhypertensive control patients undergoing cardiac catheterization. All had angiographically normal, smooth-appearing coronary arteries. Patients were matched for age and other coronary atherosclerosis risk factors. To assess endothelial cell function, the endothelium-dependent vasodilator acetylcholine (ACh, 0.01, 0.1, and 1.0 microM) and the endothelium-independent vasodilator nitroglycerin (40 micrograms) were selectively infused into the left anterior descending or circumflex coronary artery. Diameter change (expressed as percent) was assessed using quantitative angiography. There was a marked vasoconstrictor response to serial doses of ACh in hypertensive patients (-7%, -21%, and -27%) compared with control patients (-4%, -5%, and -7%) (p less than 0.02). The vasodilator response to nitroglycerin was preserved in hypertensive patients (+29%) and control patients (+25%) (p = NS), suggesting that endothelial cell dysfunction accounted for the differences in response to ACh. Thus, patients with hypertension have an accentuated coronary vasoconstrictor response to ACh, suggesting that endothelium-mediated regulation of coronary vascular tone is impaired by essential hypertension. This may reflect more generalized coronary endothelial changes contributing to the pathogenesis of atherosclerosis as well as hypertension.
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PMID:Epicardial coronary artery responses to acetylcholine are impaired in hypertensive patients. 151 54

In isolated blood vessels, acetylcholine releases endothelium-derived relaxing factor (EDRF). In vivo, the vasodilator action of acetylcholine may be mediated by EDRF, but prostacyclin or prejunctional inhibition of adrenergic neurotransmission may also be involved. Therefore, we investigated whether acetylcholine releases EDRF in humans in vivo and, if so, whether the response altered in essential hypertension. Acetylcholine was infused into the brachial artery, and forearm blood flow measured by venous occlusion plethysmography. In control subjects, acetylcholine (0.02-16 micrograms/min/100 ml tissue) increased flow from 2.4 +/- 5.0 to 20.6 +/- 5.2 ml/min/100 ml tissue (n = 14; p less than 0.05) and decreased forearm vascular resistance from 42.0 +/- 4.1 to 6.0 +/- 1.4 units (p less than 0.03), a response comparable to that of sodium nitroprusside (0.6 micrograms/min ml tissue). Acetylsalicylic acid (500 mg i.v.) given to block vascular prostacyclin production did not alter the response (n = 14). alpha-Adrenoceptor blockade by phentolamine (12 micrograms/min/100 ml tissue) did not prevent the increase in flow evoked by acetylcholine. In hypertensive patients, the decrease in forearm vascular resistance induced by acetylcholine but not evoked by sodium nitroprusside was reduced as compared with controls (14.5 +/- 3.1 and 6.1 +/- 1.6 units, respectively; n = 8; p less than 0.05). Thus, the vascular effects of acetylcholine in the human forearm circulation are independent of prostaglandins and adrenergic neurotransmission and therefore are most likely to be mediated by EDRF; the acetylcholine-induced release of EDRF is blunted in patients with essential hypertension.
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PMID:Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo. Blunted response in essential hypertension. 234 73

To assess factors responsible for phasic behavior of renal blood flow in essential hypertension, we applied an analytic method based on the estimation of power spectral density to xenon transit through the kidney and examined the renal vasodilator response to a range of agents in 53 normal subjects and 53 patients with essential hypertension. The renal vasodilator response to the calcium channel blocking agent diltiazem, but not the response to alpha-adrenergic blockade (phentolamine) or angiotensin converting enzyme inhibition (teprotide or captopril), was associated with a significant reduction in the amplitude of renal vasomotion. Acetylcholine, a vasodilator that acts through the release of a vasorelaxant factor or factors from endothelium, induced an unanticipated increase in renal vasomotion. These observations further dissociate factors responsible for basal renal vascular tone and periodic changes in renal vascular tone and raise the possibility that abnormalities in the flux of calcium into renal arterioles contribute to increased renal vasomotion in essential hypertension.
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PMID:Renal vasomotion in essential hypertension: influence of vasodilators. 273 40

Acetylcholine (ACh) is localized in the syncytiotrophoblast layer of the human placental villous tissue. An attempt was made to correlate the ACh synthesis in different pathological placentas with the histopathology of the syncytiotrophoblast available in the literature. The ACh synthesis was estimated by 'in vitro' incubation of the placental tissue. Full-term (36-38 weeks) vaginally delivered pathological placentas and hydatid moles (28 weeks) were compared with normal placentas of the same age. The results suggested that: ACh synthesis is normal in states with normal syncytiotrophoblast (e.g., healthy greater than 42 week placenta, placenta praevia, twins, and hydramnios); high ACh synthesis is correlated with hormonal and immunological changes (e.g., diabetes mellitus and Rh-incompatibility); low levels of ACh synthesis occur in states with moderate syncytial degeneration (e.g., nephrotic syndrome and essential hypertension); very poor ACh synthesis occurs when syncytial degeneration is advanced (e.g., preeclampsia, eclampsia, intra-uterine death of fetus, vesicles of hydatid mole and placental tissue infarcts); and ACh synthesis is nil in material that is completely devoid of syncytiotrophoblast (e.g., placental tissue-like material, which rarely appears in between the vesicles of hydatid moles). In essence, the degree of reduction in ACh synthesis seems to correlate with the state of the syncytiotrophoblast in various pathological conditions; and ACh synthesis is greatly reduced during syncytial degeneration. It is concluded that the capacity of the placenta to synthesize ACh reflects the state of the syncytiotrophoblast.
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PMID:A correlative review of acetylcholine synthesis in relation to histopathology of the human syncytiotrophoblast. 379 52

Essential hypertension is associated with impaired endothelium-dependent vasodilation caused by oxygen free radical-induced nitric oxide (NO) breakdown. Because calcium antagonists can improve endothelial function in patients with essential hypertension, in this study we tested the hypothesis that this beneficial effect could be related to restoration of NO availability by antioxidant properties. In 15 healthy subjects and 15 hypertensive patients, we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (ACh; 0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute), an endothelium-dependent vasodilator in basal conditions, during infusion of N:(G)-monomethyl-L-arginine (L-NMMA, 100 microg/100 mL forearm tissue per minute), an NO-synthase inhibitor, vitamin C (8 mg/100 mL forearm tissue per minute), and finally, simultaneous infusion of L-NMMA and vitamin C. The response to sodium nitroprusside (SNP; 1, 2, and 4 microg/100 mL forearm tissue per minute) was also evaluated. In control subjects, vasodilation to ACh was inhibited by L-NMMA and not changed by vitamin C. In hypertensive patients, vasodilation to ACh was blunted as compared with control subjects and resistant to L-NMMA. Vitamin C, which decreased plasma isoprostanes and increased plasma antioxidant capacity, increased the response to ACh and restored the inhibiting effect of L-NMMA. In hypertensive patients, the study was repeated after 3-month treatment with nifedipine gastrointestinal therapeutic system (30 to 60 mg/daily). Nifedipine treatment decreased circulating plasma lipoperoxides and isoprostanes and increased plasma antioxidant capacity. Moreover, nifedipine increased the vasodilation to ACh but not to SNP and restored the inhibiting effect of L-NMMA on ACh-induced vasodilation, whereas vitamin C no longer exerted its facilitating activity. These results indicate that nifedipine increases endothelium-dependent vasodilation by restoring NO availability, an effect probably determined by antioxidant activity.
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PMID:Restoration of nitric oxide availability after calcium antagonist treatment in essential hypertension. 1124 22

Age-related endothelial dysfunction could be caused by an alteration in the L-arginine-NO system and the production of oxidative stress in both normotensive and hypertensive individuals. In 47 normotensive subjects and 49 patients with essential hypertension, we evaluated forearm blood flow (by strain-gauge plethysmography) modifications induced by intrabrachial sodium nitroprusside (1, 2, and 4 microg/100 mL per minute) and acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute), an endothelium-independent vasodilator and an endothelium-dependent vasodilator, respectively. Acetylcholine was repeated in the presence of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 100 microg/100 mL per minute), the antioxidant vitamin C (8 mg/100 mL per minute), or both. Vasodilation to acetylcholine, but not to sodium nitroprusside, was lower (P<0.01) in hypertensive patients compared with control subjects. Moreover, in both groups, endothelium-dependent vasodilation declined with aging. In normotensive subjects, the inhibiting effect of L-NMMA on response to acetylcholine decreased in parallel with advancing age, whereas vitamin C increased vasodilation to acetylcholine in only the oldest group (age >60 years). In young hypertensive patients (age <30 years), vasodilation to acetylcholine was sensitive to L-NMMA, whereas in hypertensive patients age >30 years, vitamin C enhanced endothelium-dependent vasodilation and restored the inhibiting effect of L-NMMA on response to acetylcholine. In normotensive individuals, an earlier primary dysfunction of the NO system and a later production of oxidative stress cause age-related reduction in endothelium-dependent vasodilation. These alterations are similar but anticipated in hypertensive patients compared with normotensive subjects.
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PMID:Age-related reduction of NO availability and oxidative stress in humans. 1150 89

The relationship among inflammation (plasma high-sensitivity C-reactive protein [CRP]), endothelial function (hemodynamic response to acetylcholine [ACh] in the forearm), and renal function (serum creatinine and GFR [Modification of Diet in Renal Disease formula]) was investigated in 264 never-treated individuals with uncomplicated essential hypertension and serum creatinine within the normal range. Multiple regression models of renal function (creatinine) were constructed in sequence including Framingham risk factors as well the hemodynamic response to ACh and plasma CRP. The inclusion of endothelial function into a model based on Framingham risk factors added highly significant (P < 0.001) power to this model (+5%). Of note, in an alternative model that included CRP (instead of endothelial function), the creatinine variance explained by this factor was two times higher (+10%) than that associated with endothelial function in the first model. In the full model that included both endothelial function and CRP, CRP maintained a much stronger independent link with the outcome measure than endothelial function. In individuals with untreated, uncomplicated essential hypertension, multivariate modeling indicated that inflammation is a crucial mechanism mediating the endothelial-renal function link. The proatherogenic potential of inflammation associated with subtle impairment in renal function may contribute to the cardiovascular risk of essential hypertension.
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PMID:Inflammation as a mediator of the link between mild to moderate renal insufficiency and endothelial dysfunction in essential hypertension. 1656 50

We evaluated the possible role of NO in modulating tissue plasminogen activator (t-PA) release in the forearm microcirculation of normotensive subjects and hypertensive patients. Essential hypertensive patients are characterized by endothelial dysfunction because of a reduced NO availability and also show an impaired t-PA release. In healthy volunteers and essential hypertensive patients, we studied local t-PA release and forearm blood flow changes (strain-gauge plethysmography) induced by intrabrachial administration of acetylcholine (0.45 and 1.5 microg/100 mL/min) and of sodium nitroprusside (0.5 and 1.0 microg/100 mL/min), an endothelium-dependent and -independent agonist, respectively. Acetylcholine was also repeated in the presence of intra-arterial infusion of the NO synthase inhibitor N(G)-monomethyl-l-arginine (100 microg/100 mL/min). In normotensive subjects, vasodilation to acetylcholine was blunted by N(G)-monomethyl-l-arginine. In these subjects, acetylcholine infusion induced a significant, dose-dependent increase in net forearm t-PA release. N(G)-monomethyl-l-arginine significantly reduced basal t-PA release, as well as acetylcholine-induced t-PA release. In essential hypertensive patients, vasodilation to acetylcholine was reduced as compared with controls and resistant to N(G)-monomethyl-l-arginine. In contrast to what was observed in healthy control subjects, in hypertensive patients, acetylcholine had no effect on t-PA release. Similarly, N(G)-monomethyl-l-arginine failed to modify either the tonic or the agonist-induced t-PA release. Both tonic and agonist-induced release of NO are directly involved in t-PA release by endothelial cells. Essential hypertension, characterized by a reduction in tonic and stimulated NO availability, is also associated with impaired capacity of t-PA release, suggesting a major role of impaired NO availability in worsening both vasodilation and t-PA release.
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PMID:Nitric oxide modulates tissue plasminogen activator release in normotensive subjects and hypertensive patients. 1733 40

The cardiovascular effects of Persea americana Mill (Lauraceae) aqueous leaf extract (PAE) have been investigated in some experimental animal paradigms. The effects of PAE on myocardial contractile performance was evaluated on guinea pig isolated atrial muscle strips, while the vasodilatory effects of the plant extract were examined on isolated portal veins and thoracic aortic rings of healthy normal Wistar rats in vitro. The hypotensive (antihypertensive) effect of the plant extract was examined in healthy normotensive and hypertensive Dahl salt-sensitive rats in vivo. P americana aqueous leaf extract (25-800 mg/ml) produced concentration-dependent, significant (p < 0.05-0.001), negative inotropic and negative chronotropic effects on guinea pig isolated electrically driven left and spontaneously beating right atrial muscle preparations, respectively. Moreover, PAE reduced or abolished, in a concentration-dependent manner, the positive inotropic and chronotropic responses of guinea pig isolated atrial muscle strips induced by noradrenaline (NA, 10(-10)-10(-5) M), and calcium (Ca(2+), 5-40 mM). PAE (50-800 mg/ml) also significantly reduced (p < 0.05-0.001) or abolished, in a concentration-dependent manner, the rhythmic, spontaneous, myogenic contractions of portal veins isolated from healthy normal Wistar rats. Like acetylcholine (ACh, 10(-8)-10(-5) M), the plant extract (25- 800 mg/ml) produced concentration-related relaxations of isolated endothelium-containing thoracic aortic rings pre-contracted with noradrenaline. The vasorelaxant effects of PAE in the isolated, endothelium-intact aortic rings were markedly inhibited or annulled by N(G)-nitro-L-arginine methyl ester (L-NAME, 10(-5) M), a nitric oxide synthase inhibitor. Furthermore, PAE (25-400 mg/kg iv) caused dose-related, transient but significant reductions (p < 0.05-0.001) in the systemic arterial blood pressure and heart rates of the anaesthetised normotensive and hypertensive rats used. The results of this laboratory animal study indicate that PAE caused bradycardia, vasorelaxation and hypotension in the mammalian experimental models used. The vasorelaxant action of PAE was endothelium dependent, and was, therefore, possibly dependent on the synthesis and release of nitric oxide (NO). The vasorelaxant effects of PAE appeared to contribute significantly to the hypotensive (antihypertensive) effects of the plant extract. However, the findings of this study tend to suggest that P americana leaf could be used as a natural supplementary remedy in essential hypertension and certain cases of cardiac dysfunctions in some rural Africa communities.
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PMID:Cardiovascular effects of Persea americana Mill (Lauraceae) (avocado) aqueous leaf extract in experimental animals. 1749 42

We investigated the relationship between microalbuminuria (an indicator of systemic and renal endothelial dysfunction), inflammation (high-sensitivity C-reactive protein [CRP]) and endothelial function (hemodynamic response to acetylcholine [ACh] in the forearm) in 110 never-treated subjects with uncomplicated essential hypertension and serum creatinine within the normal range. Microalbuminuria was associated with the hemodynamic response to ACh (r=0.27, p=0.006) and with serum creatinine (r=0.34, p<0.001), and these associations held true in multivariate analyses. On the other hand, microalbuminuria was largely independent of serum CRP. Since microalbuminuria, response to ACh and serum CRP are all considered risk factors for renal insufficiency and since these factors were significantly related to creatinine at univariate analysis, we tested their association with creatinine in a multiple regression model including also the full set of Framingham risk factors. In this analysis, serum CRP and microalbuminuria maintained a significant association with serum creatinine, while the hemodynamic response to ACh lost substantial predictive value for serum creatinine. In conclusion, microalbuminuria in essential hypertension is weakly related to the vasodilatory response to ACh and unrelated to inflammation but maintains an independent link with serum creatinine. Collectively, these associations suggest that microalbuminuria reflects a local (renal) endothelial dysfunction and that it may contribute to renal impairment independently of inflammation and hemodynamic endothelial dysfunction in hypertensive patients.
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PMID:Microalbuminuria, endothelial dysfunction and inflammation in primary hypertension. 1805 Jan 45


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