Attenuated vasoconstrictor responses to endothelin in afferent arterioles during a high-salt diet

Endothelin-1 (ET-1) is increased in rats on a high-salt (HS) diet and participates in salt-dependent hypertension. Afferent arterioles (AA) are important for long-term blood pressure control, and therefore we hypothesized that a HS diet would alter their responsiveness to ET-1. Sprague-Dawley rats were fed either a normal-salt (NS; 0.66% NaCl) or HS (8%) diet for 1 wk. Diameters of AA were determined in response to increasing concentrations of big ET-1, ET-1, sarafotoxin 6c (S6c), or norepinephrine (NE), using the blood-perfused juxtamedullary nephron technique. ET-1 responses were also determined during blockade of endothelin type A (ETA) or type B (ETB) receptors with 10 nM ABT-627 or 30 nM A-192621, respectively. Expression of ETA and ETB receptors was determined in renal microvessels. Responses of AA to big ET-1, ET-1, and S6c were significantly attenuated during a HS diet (e.g., response to 10–10 M ET-1 in NS vs. HS rats: –52.5 ± 10.2 vs. +5.6 ± 11.3% of control diameter; P < 0.05), with no change in the responses to NE. ETB, but not ETA receptor blockade abolished the different response to ET-1 between the NS and HS groups. ETB receptor expression in renal microvessels was increased in response to HS (17.7 ± 2.4 vs. 6.6 ± 3.0% of beta-actin, P = 0.02), whereas ETA receptor expression was unchanged. These results suggest that the reduced vasoconstrictor response of AA to endothelin peptides during a HS diet is mediated by increased vasodilatory function of endothelial ETB receptors. By preserving renal blood flow, this may be an important mechanism to restore sodium balance during a HS diet

A true champion of Hungarian kidney research and nephrology education — Tribute to László Rosivall

This article pays tribute to the tremendous achievements of Dr. László Rosivall in renal (patho)physiology research and nephrology education in Hungary on the occasion of his 60th birthday. For the past several decades Dr. Rosivall has been a charismatic leader of academic institutions, national and international societies, foundations in physiology, nephrology and hypertension, but the most important of his many contributions, is his role as a scientist. He earned his MD with Summa cum Laude at Semmelweis University (1973) and was invited immediately after that to join the laboratory of Hársing. He studied the distribution of intra-renal blood flow employing then state-of-the-art methods as well as developed his own technique at Semmelweis University and at the University of Bergen with Knut Aukland. This led to his PhD thesis and degree in 1980. An important determinant of his early basic scientific training and development was his postdoctoral research fellowship and later many visiting professorships in the Nephrology Research and Training Center (NRTC) at the University of Alabama at Birmingham, Birmingham, AL, USA between 1981 and 1983. Actually, this research fellowship not only impacted his own future career, but it also cleared the path for many other young Hungarian scientists who later trained with Dr. Rosivall and then at UAB. The early 1980s were the years of significant scientific discoveries and the NRTC team at UAB made important contributions by their studies on renal and glomerular hemodynamics, the renin-angiotensin system (12, 19, 22) and by the development of classic experimental techniques like renal micropuncture, microperfusion, and the juxtamedullary nephron preparation (3) that are still being used worldwide. When Dr. Rosivall joined UAB in the 1980s, the team at the NRTC included Drs. Navar, Bell, Inscho, Carmines, Casellas, and Oparil, among many others, who share their fond memories of working with Dr. Rosivall in this article