Plasma endothelin levels in hypertension and chronic renal failure.

Abstract

Endothelin-l is a novel endothelium-derived vasoconstrictive peptide. Using a highly specific and sensitive radioimmunoassay for endothelin-l, plasma levels of immunoreactive endothelin-I were measured in 32 research subjects with normal renal function (21 normal subjects and II patients with essential hypertension), 24 patients with nondialyzed chronic renal failure, and 51 patients undergoing maintenance hemodialysis. Although there was no significant difference in plasma immunoreactive endothelin-l levels among the three groups, patients with essential hypertension had significantly higher plasma endothelin-l levels than normal subjects (2.29±1.09 vs. 1.41+0.50 pg/ml,p<0.025). When nondialyzed and hemodialyzed patients were divided into hypertensive and normotensive groups, the nondialyzed hypertensive group (n=17) had higher plasma endothelin-l levels than the comparable normotensive group (n=7) (3.08±3.43 vs. 0.73±0.34 pg/ml, p<0.05), and the hemodialyzed hypertensive group (n=18) had higher plasma endothelin-l levels than the comparable normotensive group (n=33) (2.66±1.92 vs. 1.35±0.73 pg/ml,p<0.005). Plasma atrial natriuretic factor, arginine vasopressin, renin activity, and aldosterone concentration did not show significant differences between hypertensive and normotensive individuals or a correlation with plasma endothelin-l levels. These data suggest that circulating endothelin-l may be partly involved in the development or maintenance of hypertension in humans. We recently demonstrated the presence of ET-1-like immunoreactivity (ET-LI) in normal human plasma with a highly sensitive and specific radioimmunoassay (RIA), 8 suggesting its potential role as a circulating vasoconstrictor. However, no information From the Second Department of Internal Medicine, Tokyo Medical and Dental University, Kitasato Biochemical Laboratories, SMI-Bristol Ltd. Sagamihara, Kanagawa, Tokyo Metropolitan Tama Geriatric Medical Center, Tokyo, and Shimoochiai Clinic, Shinjuku-ku, Tokyo, Japan.Address for correspondence: Yukio Hirata, MD, Endocrine Division, Second Department of Internal Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113, Japan.Received October 6, 1989; accepted in revised form January 23, 1990.is yet available as to its pathophysiological role in hypertension. Therefore, the present study was designed to determine plasma ET-LI in normal subjects and in patients with essential hypertension as well as those with chronic renal failure with or without hypertension. Methods SubjectsThe study population consisted of 21 normal individuals (11 men and 10 women), 11 patients with essential hypertension (seven men and four women), 24 patients with nondialyzed chronic renal failure (18 men and six women), and 51 patients undergoing maintenance hemodialysis (34 men and 17 women). Informed consent was obtained from each subject. Essential hypertension was defined as elevated blood pressure while in a sitting position, exceeding 160/95 mm Hg, for three consecutive measurements over a pe...

Acute blockade by endothelin-1 of haemodynamic insulin action in rats

“…Endothelin-1 is a locally produced vasoactive peptide released from vascular endothelial cells, plasma levels of which are often elevated in patients with hypertension, obesity, type 2 diabetes, peripheral vascular resistance as well as other disease states associated with cardiovascular disease [1][2][3][4][5][6]. In addition, endothelin-1 release may be stimulated by insulin, and may be involved in maintaining vasomotor tone at rest and during insulin stimulation [4,7].…”

“…Since plasma levels of endothelin-1 are elevated in various states of insulin resistance [1][2][3][4][5][6], the aim of this study was to test the hypothesis that elevated plasma levels of endothelin-1 may prevent full perfusion of muscle, thereby limiting delivery of insulin and glucose and contributing to insulin resistance. Our approach was to examine the effect of endothelin-1 infusion (both alone and in conjunction with insulin infusion) in vivo on femoral blood flow (FBF) and muscle capillary perfusion, muscle glucose uptake, and whole-body glucose infusion rate (GIR).…”

Visualization of Renal Microcirculation in Isolated Munich-Wistar Rat Kidneys: Effects of Endothelin-1 on Renal Hemodynamic Activity

“…Furthermore, Kon et al (21), who used anti-ET antibodies in an ischemic kidney model intending to deactivate endogenous ET, suggested that this peptide was involved in the onset of acute renal ischemic injury. Plasma levels of ET-1 have been shown to be elevated in patients undergoing hemodialysis treat ment and in patients with acute or chronic renal failure (4,(22)(23)(24). Thus, although these studies show that ET-1 plays an important role in renal function and disease, we still have little information derived from the direct obser vation of physiological and pathophysiological states related to ET-1 in the kidney.…”

Participation of renal and circulating endothelin in salt-sensitive essential hypertension

“…79 Reports on plasma endothelin in essential hypertension have been controversial, with increased levels published by some, 80,81 but not all investigators. 82,83 It has now become evident that two reasons account for this apparent controversy. First, plasma endothelin tends to be elevated when hypertension is severe, with concomitant end organ damage.…”