Human Artery Stenosis Research Articles

Renin, genes, microRNAs, and renal mechanisms involved in hypertension.

Renin was discovered by Robert Tigersted in 1898.1 A half century later, Pickering rediscovered renin2 and implicated it in Goldblatt’s model of renal hypertension3 that resembles renal artery stenosis in humans. In the 1960s, Borst argued that the primary defect responsible for essential hypertension resided in the kidney.4 Guyton provided support for this concept in the 1970s by means of physiological experiments and computer modeling.5 Dahl showed that kidneys transplanted from genetically hypertensive rats to a normotensive strain raised blood pressure (BP), and kidneys from normotensive rats lowered BP when transplanted into hypertensive rats.6 This suggested that the cause of hypertension was a genetic defect in the kidney. Support for this in humans was provided by Lifton, who showed that mutations in single genes involved in BP control by the kidney were responsible for rare monogenic forms of hypertension.7 Laragh and Sealey argued that in essential hypertension, plasma renin levels, even when below normal, were nevertheless too high for the prevailing BP, that is, were insufficiently suppressed, so implicating renin in hypertension.8,9 Recent reviews have highlighted the large body of experimental findings in support of abnormalities in renal processes being responsible for hypertension.10–13 The involvement of an intrarenal renin–angiotensin system now seems to be an important component of the pathophysiological mechanisms involved in essential hypertension.12–19 In the present review, I will first provide a brief summary of my earlier contributions to the hypertension field, these having been addressed in more detail in a review arising from my Lewis K. Dahl Memorial Lecture in 2010.20 I will then review my more recent research, which has involved the determination of alterations in gene expression at the transcriptome-wide level in hypertension and the pivotal mechanistic insights …

Diagnosis and management of fibromuscular dysplasia: an expert consensus

Diagnosis and management of fibromuscular dysplasia: an expert consensus

Pulse transmission coefficient: a novel nonhyperemic parameter for assessing the physiological significance of coronary artery stenoses

ObjectivesWe sought to test the hypothesis that the pulse transmission coefficient (PTC) can serve as a nonhyperemic physiologic marker for the severity of coronary artery stenosis in humans. BackgroundCoronary lesions may impair the transmission of pressure waves across a stenosis, potentially acting as a low-pass filter. The PTC is a novel nonhyperemic parameter that calculates the transmission of high-frequency components of the pressure signal through a stenosis. Thus, it may reflect the severity of the coronary artery stenosis. This study was designed to examine the correlation between PTC and fractional flow reserve (FFR) in patients with coronary artery disease. MethodsPressure signals were obtained by pressure guidewire in 56 lesions (49 patients) in the nonhyperemic state and were analyzed with a new algorithm that identifies the high-frequency components in the pressure signal. The PTC was calculated as the ratio between the distal and proximal high-frequency components of the pressure waveform across the lesion. The FFR measurements were assessed with intracoronary adenosine. ResultsThere was a significant correlation between PTC and FFR (r = 0.81, p < 0.001). By using a receiver operating characteristic analysis, we identified a PTC < 0.60 (sensitivity 100%, specificity 98%) to be the optimal cutoff value for predicting an FFR < 0.75. ConclusionsPulse transmission coefficient is a novel nonhyperemic parameter for the physiologic assessment of coronary artery stenoses. It correlates significantly with FFR and may predict an FFR < 0.75 with high accuracy. Pulse transmission coefficient may be useful as an adjunct measurement to FFR, especially in patients with microcirculatory disease and impaired maximal hyperemia.

The Antiaggregating and Antithrombotic Activity of Clopidogrel Is Potentiated by Aspirin in Several Experimental Models in the Rabbit

It is unknown whether the addition of aspirin might increase both the efficacy and the potency of clopidogrel, a potent and selective ADP blocker. For that purpose, the efficacy of clopidogrel (1-20 mg/kg, p.o.) administered orally to rabbits alone or in combination with aspirin (0.1-10 mg/kg, p.o.) was determined in several experimental models. A potent synergistic effect of the clopidogrel/aspirin association was demonstrated with regard to collagen-induced platelet aggregation measured ex vivo. Similarly, aspirin potentiated the antithrombotic activity of clopidogrel measured with regard to experimental thrombosis induced by a silk thread or on stents placed in an arteriovenous shunt, thrombus formation following electrical stimulation of the rabbit carotid artery and with regard to 111In-labeled platelet deposition on a stent implanted in an arteriovenous shunt or on the subendothelium following air drying injury of the rabbit carotid artery. A similar potentiating effect of aspirin was obtained with regard to myointimal proliferation (restenosis) in the femoral arteries of atherosclerotic rabbits which occurred as a consequence of stent placement. The clopidogrel/aspirin combination showed only additive-type effects on bleeding time prolongation induced by ear transection in the rabbit, therefore showing that combined inhibition of cyclooxygenase and ADP's effects provide a marked enhanced antithrombotic efficacy. Such a combination may provide substantial protection against platelet aggregation leading to thrombotic occlusion at sites of endothelial injuries and coronary artery stenosis in humans.

Change in pressor responsiveness to angiotensin II as a determinant of blood pressure after unclipping in two-kidney, one clip hypertensive rats.

The hypotensive effect of correction of renal artery stenosis in humans or experimental animals with renovascular hypertension is commonly attributed to decreasing renin secretion from the formerly stenotic kidney. However, plasma renin activity is normal in 50% of individuals with renovascular hypertension. We studied conscious, chronically instrumented two-kidney, one clip (2K1C) rats. The renal artery clip was removed and mean arterial pressure measured for 3 days. The majority of the fall in blood pressure occurred between 2 and 48 hours after unclipping. Measurement of water balance and urinary sodium excretion revealed no effect of unclipping. In another experiment, 2K1C hypertensive rats were chronically treated with enalapril and concomitant infusion of angiotensin II (3.8 pmol/min [4 ng/min] IV) to maintain blood pressure at hypertensive levels and prevent a fall in angiotensin II levels on unclipping. After 5 days, the clip was removed or sham removed, and treatment was continued. Blood pressure was recorded for 7 days. Blood pressure remained elevated in the sham unclipped rats. Unclipped rats exhibited a dichotomous response; blood pressure fell significantly within 48 hours in the majority of rats (responders) but remained elevated in a minority (nonresponders). All treatment was then withdrawn for 2 days. Sham unclipped rats remained hypertensive, and responders exhibited a further small decline in blood pressure. Blood pressure fell to normal in the nonresponders. Blood pressure falls after correction of renal artery stenosis in renovascular hypertension in part because of a decrease in pressor responsiveness to angiotensin II.

Noninvasive Carotid Artery Testing: A Meta-analytic Review

To compare the operating characteristics of six noninvasive tests for carotid artery stenosis. A structured search was done using MEDLINE, reference lists from selected articles, and bibliographies from neurology textbooks that focused on the diagnosis of carotid artery stenosis in humans. The search yielded 568 articles. Articles were selected if the noninvasive test results they presented used carotid angiography as the reference standard for comparison, if carotid artery occlusion was considered as a separate category, and if contingency tables could be constructed. At least two physicians reviewed all selected articles. Items abstracted included patient demographics, study design, sites of patient enrollment, whether the interpretation of test outcomes was blinded, and specific results. Sensitivity, specificity, receiver operating characteristic (ROC) curves, and summary measures of effectiveness for each test were calculated. Carotid duplex ultrasonography, carotid Doppler ultrasonography, and magnetic resonance angiography have sensitivities between 0.82 and 0.86, specificities at 0.98, and test-effectiveness measures at or exceeding 3.0 when predicting 100% occlusion. For carotid stenosis of 70% or more, these three tests and supraorbital Doppler ultrasonography all have sensitivities of 0.83 to 0.86, specificities of 0.89 to 0.94, test-effectiveness measures approaching 3.0, and composite ROC areas of 0.91 to 0.92. Limiting analysis to studies that enrolled consecutive patients and those in which interpretation of the noninvasive tests was independent of the angiograms did not substantially change our results. Carotid duplex ultrasonography, carotid Doppler ultrasonography, and magnetic resonance angiography are all similarly successful at predicting 100% carotid artery occlusion and 70% stenosis. Other factors, such as cost, availability, and local experience may influence the decision to use these tests to screen for carotid artery atherosclerosis that may respond to surgery.