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• W2034972476 abstract "Abstract Attenuated cholinergic vasodilatation has been suggested as an endothelium-related mechanism involved in essential hypertension. We investigated the role of muscarinic (M) receptor subtypes in the forearm resistance vasculature. In eight white men with essential hypertension and eight matched normotensive control subjects (age of both groups, 47±4 years; mean±SEM), we infused the nonselective agonist methacholine in the presence of saline and the antagonists atropine (nonselective), pirenzepine (M 1 -selective), and AF-DX 116 (M 2 -selective) into the brachial artery and measured forearm blood flow and forearm vascular resistance using venous occlusion plethysmography. Affinity constants (pK b values) were determined from calculated plasma concentrations of the infused compounds and EC 50 values. Sodium nitroprusside was given as an endothelium-independent control, and minimal forearm vascular resistance after 10 minutes of ischemia was used as a marker of structural vascular changes. Hypertensive patients showed higher minimal forearm vascular resistance, indicating structural vascular changes. However, sodium nitroprusside– and methacholine-induced vasodilatation was similar in both groups, with apparent EC 50 values (log moles per liter; mean±SEM) of −7.32±0.13 and −7.51±0.21 in hypertensive patients and −7.37±0.13 and −7.45±0.02 in control subjects, respectively. Atropine, pirenzepine, and AF-DX 116 caused a shift to the right of the concentration-response curve of methacholine, with apparent pK b values of 8.63±0.08, 6.81±0.13, and 5.51±0.29 in hypertensive individuals and 8.62±0.10, 6.98±0.08, and 5.49±0.09 in control subjects, respectively. Again, there were no statistically significant differences in these pharmacological parameters between hypertensive patients and normotensive subjects. The affinity constants and rank order for potency of the muscarinic antagonists, atropine>pirenzepine>AF-DX 116, indicate that cholinergic vasodilatation in the forearm vascular bed is predominantly mediated by the M 3 receptor subtype. Despite indications for structural vascular changes in hypertensive subjects, the vasodilator responses to both sodium nitroprusside and methacholine were unchanged in these patients. Essential hypertension is not associated with changes in the pharmacological characteristics of muscarinic receptors in forearm resistance vasculature." @default.
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• W2034972476 date "1995-07-01" @default.
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• W2034972476 title "In Vivo Characterization of Muscarinic Receptor Subtypes That Mediate Vasodilatation in Patients With Essential Hypertension" @default.
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• W2034972476 doi "https://doi.org/10.1161/01.hyp.26.1.70" @default.
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