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Biomedical subjects

S Taddei

Publications and source records attributed to S Taddei.

At least 55 records · Page 3Linked to original sources
PubMed2000

Effect of the angiotensin II type 1 receptor blocker candesartan on endothelial function in patients with essential hypertension.

Patients with essential hypertension are characterized by impaired basal and agonist-evoked nitric oxide release and increased endogenous endothelin (ET)-1-induced vasoconstriction. To assess whether candesartan, an angiotensin II type 1 receptor blocker, can improve endothelial function, we studied the changes in forearm blood flow (FBF) induced in 15 hypertensive patients and in 15 control subjects by the intrabrachial infusion of N(G)-monomethyl-L-arginine (L-NMMA), norepinephrine, the ET A/B receptor antagonist TAK 044, sodium nitroprusside, and acetylcholine. In hypertensive patients, the FBF study was repeated 2 and 12 months after the start of treatment with candesartan cilexetil (8 to 16 mg daily). Compared with controls (maximal FBF decrease, -46+/-11%), hypertensive patients showed a reduced (P<0.001) vasoconstrictor response to L-NMMA (maximal FBF decrease, -28+/-7%); the response to norepinephrine was only slightly impaired, and the response to sodium nitroprusside was similar to that of controls. Finally, TAK-044 caused greater vasodilation in hypertensive patients (maximal FBF increase, 77+/-9%) than in controls (maximal FBF increase, 17+/-10%). In hypertensive patients, candesartan cilexetil significantly enhanced vasoconstriction to L-NMMA after 2 and 12 months (maximal FBF decrease, 37+/-2% [P<0.05] and 42+/-2% [P<0.001], respectively). The responses to norepinephrine, acetylcholine, and sodium nitroprusside were not modified after 2 months. After 12 months, the responses to acetylcholine and sodium nitroprusside were significantly (P<0.05) enhanced at the highest rates. Vasodilation to TAK-044 was abolished after treatment with candesartan cilexetil; this effect is associated with a reduced plasma ET-1 concentration. This study demonstrated that the angiotensin II receptor blocker candesartan improves tonic nitric oxide release and reduces vasoconstriction to endogenous ET-1 in the forearm of hypertensive patients.

Acetylcholine↗
PubMed2000

Organ donation and transplantation as health programs in Italy.

Organ and tissue donation and transplantation have a role in public health programs as organizational projects designed by public health departments to increase the quality and number of donations and transplantations. These programs serve as communication projects to inform public opinion on cerebral death, organ and tissue shortages, procurement and allocation rules, and the quality of life of transplanted patients. The health department of Emilia-Romagna created a regional law and a multimedia communication program for these purposes, resulting in a 95% increase of cadaver donor in 4 years. In 1995, regional activity reached the European mean level and afterwards surpassed it. In 1997, the bone bank was activated, followed in 1998 by the heart valve and vascular segment bank. The regional health department now considers transplant activities a primary goal; human and professional relations between intensive care units and the transplant reference center are considered crucial; cooperation among health departments, medical teams involved in organ procurement and transplant activities has been fostered, and the local coordination network has been active and efficient. The public information campaign has proven important in providing information both to professionals and citizens.

Health Care Rationing↗
PubMed2000

Reliability of ultrasound screening of liver and kidney donors: a retrospective study.

The reliability of abdominal ultrasound in screening liver and kidney donors was assessed by correlating ultrasound findings with the suitability of organs for transplantation as determined by direct examination of the organs. We evaluated 100 multiorgan donors (100 livers, 200 kidneys) during a 15-month period. Abdominal ultrasound showed the following results for liver and kidney, respectively: specificity, 95.6% and 98.9%; sensitivity, 62.5% and 66.6%; and accuracy, 93% and 97%. These results show that abdominal ultrasound is a valuable tool for determining suitability of organs for transplantation when the ultrasound findings are normal. When ultrasound findings are abnormal, further studies are necessary to determine the suitability of the organs for transplantation.

Adolescent↗
PubMed1999

Vasoconstriction to endogenous endothelin-1 is increased in the peripheral circulation of patients with essential hypertension.

BACKGROUND: In humans, endothelin (ET)-1 could be implicated in the pathophysiology of several cardiovascular diseases, including essential hypertension. We therefore evaluated the role of ET-1 in control of vascular tone in essential hypertension. METHODS AND RESULTS: We used strain-gauge venous plethysmography to test changes in forearm blood flow induced by intrabrachial infusion of TAK-044 (10, 30, and 100 microgram. 100 mL(-1). min(-1)), an ET(A)/ET(B) receptor antagonist, or sodium nitroprusside (1 and 2 microgram. 100 mL(-1). min(-1)), a vasodilator that acts on smooth muscle cells, in hypertensive patients and healthy controls (n=10 in each group). The NO pathway was also evaluated by infusion of N(G)-monomethyl-L-arginine, (L-NMMA; 10, 30, and 100 microgram. 100 mL(-1). min(-1)), an NO synthase inhibitor, and norepinephrine (3, 9, and 30 ng. 100 mL(-1). min(-1)) as control. Immunoreactive plasma ET-1 was measured by radioimmunoassay. In hypertensive patients, TAK-044 caused a vasodilation that was significantly (P<0.01) increased compared with normotensive subjects. Moreover, vasoconstriction to L-NMMA was significantly (P<0.01) decreased in hypertensive patients compared with controls. In contrast, the vascular responses to sodium nitroprusside and norepinephrine, as well as levels of immunoreactive plasma ET-1, were similar in hypertensive patients and controls. In the study population, vasodilation to TAK-044 and vasoconstriction to L-NMMA showed an inverse correlation (r=-0.56, P<0.05). CONCLUSIONS: These results indicate that TAK-044 caused a greater degree of vasodilation in the forearm vessels of essential hypertensive patients compared with normotensive subjects, an alteration associated with decreased tonic NO release.

Endothelin Receptor Antagonists↗
PubMed1999

Vasodilation to bradykinin is mediated by an ouabain-sensitive pathway as a compensatory mechanism for impaired nitric oxide availability in essential hypertensive patients.

BACKGROUND: In essential hypertension, endothelium-dependent vasodilation is impaired because of reduced nitric oxide (NO) availability, which is mainly caused by oxidative stress. The present study was designed to identify the mechanism(s) responsible for NO-independent vasodilation to bradykinin in patients with essential hypertension. METHODS AND RESULTS: In 16 healthy subjects (49.5+/-5.8 years; 118.6+/-3.5/78.9+/-2.9 mm Hg) and 16 patients with essential hypertension (47.9+/-4.8 years; 154.6+/-4.5/102.9+/-3.2 mm Hg), we measured modifications in forearm blood flow (strain-gauge plethysmography) during intrabrachial infusion of bradykinin (5, 15, or 50 ng/100 mL of forearm tissue per minute) in the presence of saline, N(omega)-monomethyl-L-arginine (L-NMMA; used to inhibit NO synthase; 100 microg/100 mL of forearm tissue per minute), and ouabain (to block Na(+)K(+)/ATPase and prevent hyperpolarization; 0.7 microg/100 mL of forearm tissue per minute). In healthy subjects, vasodilatation to bradykinin was significantly blunted by L-NMMA and unaffected by ouabain. In hypertensive patients, vasodilatation to bradykinin was not modified by L-NMMA, but it was significantly reduced by ouabain. In an adjunctive group of 8 hypertensive patients (49.9+/-3.8 years; 155.9+/-5.5/103.7+/-3.9 mm Hg), the response to bradykinin was repeated during the administration of intrabrachial vitamin C (a scavenger for oxygen free radicals; 8 mg/100 mL of forearm tissue per minute). In these patients, L-NMMA-induced inhibition of vasodilation to bradykinin was restored, and ouabain was no longer effective. In a final group of 6 normotensive controls (45.9+/-4.1 years; 115.1+/-2.9/79.3+/-2.1 mm Hg), vasodilation to bradykinin residual to L-NMMA blockade was further inhibited by simultaneous ouabain infusion. CONCLUSIONS: Vasodilation to bradykinin is impaired in essential hypertensive patients because of an NO-system alteration caused by oxidative stress, and it is mediated by an alternative pathway, possibly involving endothelium-dependent hyperpolarization.

Adaptation, Physiological↗
PubMed1999

A comparison of pediatric and adult kidney donors for adult recipients.

The high demand for organs for transplantation has made it necessary to consider using even the oldest and youngest of potential donors in order to increase the organ supply. In this retrospective study, the outcome of kidney transplantation using cadaveric pediatric donors was compared with that of an adult control series. Graft procurement took place in two regions of Italy (Emilia-Romagna and Piemonte) over an 11-year period. A group of pediatric donors (< 15 years old, n = 30) was compared with an adult donor group (n = 67). All recipients were adults who received cyclosporin as immunosuppression. Actuarial patient and graft survival rates did not differ significantly between the two groups (patient survival 96% and 96% for pediatric donors versus 98% and 92% for adult donors at 1 and 5 years post-transplantation; graft survival 76% and 68% for pediatric donors versus 88% and 74% for adult donors 1 and 5 y post-transplantation). Complications were also evaluated, but no difference was found (the only exception being the creatinine level in the 5th year). Renal transplantation with cadaveric donors starting at 4 years of age gave results comparable to kidneys coming from adults. These data show that cadaveric pediatric donor kidneys may be used in adult recipients with good results. The ethical implications of the subject are extensively reviewed.

Adolescent↗
PubMed1999

Adenosine causes the release of active renin and angiotensin II in the coronary circulation of patients with essential hypertension.

OBJECTIVES: The aim of the study was to evaluate whether adenosine infusion can induce production of active renin and angiotensin II in human coronary circulation. BACKGROUND: Adenosine can activate angiotensin production in the forearm vessels of essential hypertensive patients. METHODS: In six normotensive subjects and 12 essential hypertensive patients adenosine was infused into the left anterior descending coronary artery (1, 10, 100 and 1,000 microg/min x 5 min each) while active renin (radioimmunometric assay) and angiotensin II (radioimmunoassay after high performance liquid chromatography purification) were measured in venous (great cardiac vein) and coronary arterial blood samples. In five out of 12 hypertensive patients adenosine infusion and plasma samples were repeated during intracoronary angiotensin-converting enzyme inhibitor benazeprilat (25 microg/min) administration. Finally, in adjunctive hypertensive patients, the same procedure was applied during intracoronary sodium nitroprusside (n = 4) or acetylcholine (n = 4). RESULTS: In hypertensive patients, but not in control subjects, despite a similar increment in coronary blood flow, a significant (p < 0.05) transient increase of venous active renin (from 10.7 +/- 1.4 [95% confidence interval 9.4 to 11.8] to a maximum of 13.8 +/- 2.1 [12.2 to 15.5] with a consequent drop to 10.9 +/- 1.8 [9.7 to 12.1] pg/ml), and angiotensin II (from 14.6 +/- 2.0 [12.7 to 16.5] to a maximum of 20.4 +/- 2.7 [18.7 to 22.2] with a consequent drop to 16.3 +/- 1.8 [13.9 to 18.7] pg/ml) was observed under adenosine infusion, whereas arterial values did not change. Calculated venous-arterial active renin and angiotensin II release showed a strong correlation (r = 0.78 and r = 0.71, respectively; p < 0.001) with circulating active renin. This adenosine-induced venous angiotensin II increase was significantly blunted by benazeprilat. Finally, both sodium nitroprusside and acetylcholine did not affect arterial and venous values of active renin and angiotensin II. CONCLUSIONS: These data indicate that exogenous adenosine stimulates the release of active renin and angiotensin II in the coronary arteries of essential hypertensive patients, and suggest that this phenomenon is probably due to renin release from tissue stores of renally derived renin.

Acetylcholine↗
PubMed1999

Relationship between the circulating and vascular renin-angiotensin system and the vasodilating effect of captopril in human hypertension.

A vascular renin-angiotensin system (RAS) is present in the forearm vasculature of essential hypertensive patients and is closely related to the circulating renin profile. To test whether the haemodynamic effect of acute intrabrachial administration of captopril is related to the circulating and/or vascular RAS, 31 hypertensive patients were selected and divided into four groups according to their different circulating RAS profile (n = 7 hypertensive patients with primary aldosteronism and suppressed plasma renin activity; n = 7 low renin essential hypertensive patients; n = 8 normal renin essential hypertensive patients; n = 9 high renin renovascular hypertensive patients). The forearm net balance of active renin, plasma renin activity and angiotensin II, obtained by intrabrachial infusion of the beta-adrenergic receptor agonist isoproterenol (0.03, 0.1, 0.3 microg/100 ml/min) and calculated as the product of the venous-arterial plasma concentration gradient and forearm blood flow (FBF), was closely related to the circulating RAS. Captopril (0.25, 2.5, 25 microg/100 ml/min per 20 min each dose) unchanged basal FBF in the primary aldosteronism and low renin groups (FBF increase: from 3.9 +/- 0.4 to a maximum of 4.1 +/- 0.5 and from 3.8 +/- 0.3 to a maximum of 4.3 +/- 0.5 ml/100 ml/min, respectively), whereas it caused slight vasodilation in the normal renin group (from 3.9 +/- 0.3 to a maximum of 5.3 +/- 0.7 ml/100 ml/min), and pronounced vasodilation in the high renin group (from 4.0 +/- 0.4 to a maximum of 6.4 +/- 0.5 ml/100 ml/min). Captopril-induced vasodilation showed a significant direct correlation with the circulating and vascular RAS. The present data, while confirming the existence of a vascular RAS in the forearm of hypertensive patients indicate that the acute vasodilating effect of intrabrachial captopril is linked to a stimulated RAS, either circulating or vascular, supporting the evidence that, in acute conditions, ACE inhibitors exert their vasodilating effect through the RAS blockade.

Antihypertensive Agents↗
PubMed1998

Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension.

BACKGROUND: Essential hypertension is associated with impaired endothelium-dependent vasodilation. Inactivation of endothelium-derived nitric oxide by oxygen free radicals participates in endothelial dysfunction in experimental hypertension. To test this hypothesis in humans, we evaluated the effect of antioxidant vitamin C on endothelium-dependent responses in essential hypertensive patients. METHODS AND RESULTS: In 14 healthy subjects (47.1+/-4.8 years; blood pressure, 120.6+/-4.5/80.9+/-3.5 mm Hg) and 14 essential hypertensive patients (47.3+/-5.1 years; blood pressure, 153.9+/-7.1/102.3+/-4.1 mm Hg), we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg x 100 mL(-1) x min(-1)) or sodium nitroprusside (1, 2, and 4 microg/100 mL forearm tissue per minute), an endothelium-dependent and -independent vasodilator, respectively, in basal conditions and during infusion of intrabrachial vitamin C (2.4 mg/100 mL forearm tissue per minute). In hypertensive patients but not in control subjects, vitamin C increased (P<0.01) the impaired vasodilation to acetylcholine, whereas the response to sodium nitroprusside was unaffected. Moreover, in another 14 hypertensive patients (47.1+/-5.2 years; blood pressure, 155.2+/-6.9/103.7+/-4.5 mm Hg), the facilitating effect of vitamin C on vasodilation to acetylcholine was reversed by N(G)-monomethyl-L-arginine (100 microg/100 mL forearm tissue per minute), a nitric oxide synthase inhibitor, suggesting that in essential hypertension superoxide anions impair endothelium-dependent vasodilation by nitric oxide breakdown. Finally, because in adjunctive 7 hypertensive patients (47.8+/-6.1 years; blood pressure, 155.3+/-6.8/103.5+/-4.3 mm Hg), indomethacin (50 microg/100 mL forearm tissue per minute), a cyclooxygenase inhibitor, prevented the potentiating effect of vitamin C on vasodilation to acetylcholine, it is possible that in essential hypertension a main source of superoxide anions could be the cyclooxygenase pathway. CONCLUSIONS: In essential hypertensive patients, impaired endothelial vasodilation can be improved by the antioxidant vitamin C, an effect that can be reversed by the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine. These findings support the hypothesis that nitric oxide inactivation by oxygen free radicals contributes to endothelial dysfunction in essential hypertension.

Acetylcholine↗
PubMed1998

Effects of angiotensin converting enzyme inhibition on endothelium-dependent vasodilatation in essential hypertensive patients.

BACKGROUND: Essential hypertension is characterized by an impairment of endothelium-dependent vasodilatation. OBJECTIVE: To test whether antihypertensive treatment with the angiotensin converting enzyme inhibitor lisinopril can improve vasodilatation in response to endothelium-dependent agonists in essential hypertensive patients. DESIGN AND METHODS: We studied the effect of acute (6-8 h after dosing), prolonged (1 month) and chronic (12 months) lisinopril treatment on forearm blood flow response (strain-gauge plethysmography) induced in 10 hypertensive patients (aged 43.6 +/- 8.1 years, blood pressure 151.4 +/- 6.8/99.8 +/- 3.3 mmHg) by intrabrachial infusions of 0.15, 0.45, 1.5, 4.5, and 15 microg/100 ml per min acetylcholine and 5, 15, and 50 ng/100 ml per min bradykinin, two endothelium-dependent vasodilators, and 1, 2, and 4 microg/100 ml per min sodium nitroprusside, an endothelium-independent vasodilator. At baseline, vascular response was compared with that of 10 normotensive subjects (aged 42.4 +/- 6.6 years, blood pressure 118.4 +/- 6.1/77.8 +/- 3.4 mmHg). RESULTS: Hypertensive patients had blunted (P < 0.01 or less) vasodilatations in response to infusions of acetylcholine (from 3.7 +/- 0.3 to 18.3 +/- 4.9 ml/100 ml per min) and bradykinin (from 3.7 +/- 0.4 to 15.8 +/- 2.6 ml/100 ml per min) compared with those of controls (from 3.6 +/- 0.3 to 25.3 +/- 5.2 ml/100 ml per min for acetylcholine and from 3.7 +/- 0.3 to 26.9 +/- 4.9 ml/100 ml per min for bradykinin) whereas the responses to infusion of sodium nitroprusside were similar (from 3.6 +/- 0.3 to 18.5 +/- 3.9 and from 3.6 +/- 0.3 to 16.4 +/- 1.8 ml/100 ml per min, respectively). Acute and prolonged lisinopril treatments significantly (P < 0.05 or less) improved vasodilatation in response to infusion of bradykinin (from 3.7 +/- 0.4 to 24.5 +/- 4.9 and from 3.7 +/- 0.3 to 22.1 +/- 4.9 ml/100 ml per min, respectively), but not in response to infusions of acetylcholine and of sodium nitroprusside. Chronic lisinopril treatment increased (P < 0.05) the response to infusions of not only bradykinin (from 3.5 +/- 0.5 to 27.6 +/- 5.3 ml/100 ml per min), but also of acetylcholine (from 3.5 +/- 0.5 to 27.8 +/- 8.0 ml/100 ml per min) and sodium nitroprusside (from 3.4 +/- 0.6 to 25.9 +/- 8.5 ml/100 ml per min). However, when the responses to infusions of acetylcholine and bradykinin were normalized with respect to that to infusion of sodium nitroprusside, only the vasodilatation in response to infusion of bradykinin was shown to have been increased by lisinopril treatment. CONCLUSIONS: Administration of lisinopril to patients with essential hypertension can selectively increase vasodilatation in response to infusion of bradykinin.

Acetylcholine↗
PubMed1998

The role of endothelium in human hypertension.

Endothelium-derived nitric oxide is not only a potent vasodilator but also inhibits platelet aggregation, smooth muscle cell proliferation, monocyte adhesion and adhesion molecule expression. In several pathological conditions, such as human hypertension, nitric oxide availability is reduced. This alteration has been documented in the peripheral and coronary micro- and macrocirculation and in the renal circulation. The main mechanism leading to endothelial dysfunction is production of cyclooxygenase-dependent factors, including prostanoids and oxygen free radicals, which cause nitric oxide breakdown. Dysfunctional endothelium can be one of the main mechanisms causing vascular damage, in particular, atherosclerosis; hence, an important aim for antihypertensive treatment could reside not only in normalizing blood pressure values but also in reversing endothelial dysfunction. Available evidence indicates that different classes of antihypertensive compounds have different effects on endothelial dysfunction.

Antihypertensive Agents↗
PubMed1998

Renal changes induced by nitric oxide and prostaglandin synthesis reduction: effects of trandolapril and verapamil.

The benefits of the simultaneous administration of low doses of a calcium antagonist and a converting enzyme inhibitor in the treatment of hypertension and renal vasoconstriction are well established. The objective of this study was to evaluate whether the administration of low doses of a calcium antagonist and a converting-enzyme inhibitor have beneficial effects in treating the renal alterations induced by the acute administration of a cyclooxygenase inhibitor when nitric oxide synthesis is reduced. These effects were examined in anesthetized dogs before and during an acute sodium load. It was found that the intrarenal infusion of meclofenamate (5 microg x kg[-1] x min[-1]), simultaneously with a low dose of NG-nitro-L-arginine methyl ester (1 microg x kg[-1] x min[-1]), produced a 40% decrease of renal blood flow and glomerular filtration rate and a reduction in the renal excretory response to the sodium load. In a second group of dogs, intrarenal verapamil (0.5 microg x kg[-1] x min[-1]) was effective in blocking the effects of nitric oxide and prostaglandin synthesis inhibition on sodium excretion and glomerular filtration rate but did not modify the effects on renal blood flow. An intrarenal infusion of trandolapril (0.3 microg x kg[-1] x min[-1]) was effective in a third group of dogs in reducing the renal hemodynamic effects but not in preventing the antinatriuretic effect observed in the first group. Finally, in a fourth group, the simultaneous administration of verapamil and trandolapril was effective in treating all the renal changes induced by the cyclooxygenase inhibitor when nitric oxide synthesis was reduced. These results suggest that the combination of low doses of trandolapril and verapamil has additive effects in treating the renal vasoconstriction and antinatriuresis induced by the acute administration of a cyclooxygenase inhibitor, when nitric oxide synthesis is reduced.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Endothelial function and common carotid artery wall thickening in patients with essential hypertension.

Intimal-medial thickening of the carotid wall is considered an early marker of atherosclerosis. Endothelial function is impaired in the presence of various cardiovascular risk factors that are implicated in the pathogenesis of atherosclerosis. To evaluate the relationship between vascular reactivity and carotid intimal-medial thickening, in 44 (mean+/-SD age, 45.7+/-8.8 years; range, 28 to 60 years; 31 men and 13 women) patients with essential hypertension who had never been treated and whose history of increased blood pressure was no longer than 12 months, we evaluated several parameters: intimal-medial thickening of the common carotid arteries (by B-mode ultrasound); forearm vascular response (by strain-gauge plethysmography) to intrabrachial infusion of acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL forearm tissue per minute), an endothelium-dependent vasodilator, or sodium nitroprusside (1, 2, and 4 microg/100 mL forearm tissue per minute), an endothelium-independent vasodilator; calculated minimal forearm vascular resistances (the ratio between mean arterial pressure and maximal forearm vasodilation induced by 13 minutes of ischemia and 1 minute of exercise); and left ventricular mass index (on echocardiography profile). Carotid wall intimal-medial thickening showed a significant (P<0.001) inverse correlation with vasodilation to acetylcholine (r=-0.58) and age (r=-0.40), whereas no correlation was observed with the response to sodium nitroprusside or with minimal forearm vascular resistances, left ventricular mass index, systolic and diastolic blood pressures, and plasma cholesterol and glucose levels. Moreover, vasodilation to acetylcholine showed no correlation with minimal forearm vascular resistances or left ventricular mass index. Although comparison of different vascular "districts," such as the forearm microcirculation and carotid artery, does not allow for a conclusive interpretation, the present data indicate that in patients with essential hypertension, carotid wall thickening is associated with reduced endothelium-dependent vasodilation and suggest that endothelial dysfunction might be involved in early arterial structural alterations.

Acetylcholine↗
PubMed1998

Endothelial dysfunction in hypertension: fact or fancy?

Endothelium can deeply influence vascular tone and structure. The main endothelium-derived factor is nitric oxide (NO), which not only is a potent vasodilator but also inhibits platelet aggregation, smooth muscle cell proliferation, monocyte adhesion, and adhesion molecule expression, thus protecting the vessel wall against the development of atherosclerosis and thrombosis. In human hypertension, endothelial dysfunction has been documented in peripheral and coronary macro- and microcirculation and in renal circulation. Impaired endothelium-dependent vasodilatation associated with essential hypertension appears to be a primary phenomenon because it can be detected in the offspring of essential hypertensive patients, shows no clear correlation with blood pressure value, and is not normalized by the mere reduction of blood pressure. The phenomenon responsible for endothelial alteration in essential hypertensive patients appears to be the activation of an alternative pathway involving cyclo-oxygenase (COX), which reduces NO availability through production of oxidative stress. This alteration in the NO pathway could be the main mechanism through which a dysfunctional endothelium may promote atherosclerosis and thrombosis in essential hypertension. Therefore, an important aim of antihypertensive therapy would be not only to normalize blood pressure values but also to reverse endothelial dysfunction by restoring NO availability. Evidence indicates that different classes of antihypertensive compounds have different effects on this alteration. Dihydropiridine calcium antagonists appear to act specifically on the NO pathway by a mechanism that is probably related to antioxidant activity.

Endothelium, Vascular↗
PubMed1997

Insulin sensitivity, vascular reactivity, and clamp-induced vasodilatation in essential hypertension.

BACKGROUND: Insulin resistance and vascular abnormalities have both been described in patients with essential hypertension. Whether these defects are associated with one another in the same individual has not been established. METHODS AND RESULTS: Whole-body insulin sensitivity (by the insulin clamp technique), forearm minimal vascular resistances, and the dose-response curve to acetylcholine, sodium-nitroprusside, and norepinephrine were measured in a group of 29 male patients with untreated essential hypertension. When the patients were divided into tertiles according to their level of insulin sensitivity, resistant and sensitive hypertensives were matched on several potential confounders of insulin action and vascular function. These subgroups showed similar minimal vascular resistances (2.5+/-0.2 versus 3.2+/-0.6 mm Hg per mL x min(-1) x dL(-1)) and superimposable responses to graded intraarterial infusions of acetylcholine, sodium-nitroprusside, and norepinephrine. No correlation was found between the vascular parameters (slope of the curve or maximal response) and insulin-mediated glucose uptake in the whole group. During the clamp, insulin sensitive patients tended to have greater increments in forearm blood flow when compared to their insulin resistant counterparts (+53+/-21 versus +9+/-7%, P=.06); in the whole group, clamp-induced vasodilatation was weakly related to insulin-mediated glucose uptake (r=.44, P<.02) as well as to the slope of the acetylcholine dose-response curve (r=.40, P<.04). Together, these two responses explained 30% (multiple r=.55, P<.01) of the variability in insulin-induced vasodilatation. CONCLUSIONS: Metabolic insulin resistance in essential hypertension is not associated with abnormalities in vascular structure, acetylcholine or nitroprusside-induced vasodilatation, or vascular adrenergic reactivity. Degree of insulin sensitivity and acetylcholine sensitivity explain a small portion of the variability of the clamp-induced vasodilatation in hypertensive patients.

Acetylcholine↗