the putative renal medullary depressor hormone: medullipin rises like phoenix from the ashes?

1
Editor’s Choice Capillary growth in response to exercise training is retained in ageing human skeletal muscle and can be demonstrated non-invasively ÔMicrovascular filtration rate and microvascular tortuosity changed in like manner after exercise training in the elderly suggesting a preserved adaptation capacityÕ. In skeletal muscles, an increase in capillary numbers is a hallmark of adaptation to endurance exercise training, contributing to increased aerobic capacity. This has been shown in both young and elderly humans based usually on the analysis of inva- sively obtained muscle biopsies. The study by Charles and colleagues in this issue has employed a non-invasive method of evaluating fluid filtration rate in human lower limbs as an index of microvascular exchange surface area and compared it to histological data on capillarity from quadriceps muscle biopsy samples in elderly men (mean age 74 years) undertaking a 14 week endurance exercise training programme. Peak oxygen consump- tion increased by 11%, muscle citrate synthase activity by 28% and calf reactive hyperaemia by 21%, con- firming training effects. In muscle biopsies, the length of microvessel wall in contact with the muscle fibre peri- meter increased 26% overall after training, while calf microvascular fil- tration rate determined non-invasively by venous occlusion plethysmography increased by 79%. Within all subjects, the two indices correlated significantly implying a common effect of training on exchange surface area albeit in different leg muscles. Increased contact length between microvessels <15 lm diameter and fibres in muscle cross- sections also suggests that growth has occurred by transverse sprouting and/ or lengthening of existing vessels. M. D. Brown School of Sport and Exercise Sciences, University of Birmingham, Birmingham, UK [email protected] Guest editor The putative renal medullary depressor hormone: medullipin rises like Phoenix from the ashes? ÔThe vasodepressor principle is con- tained in the kidney medulla, but not in the cortex. It can be separated from endogenous emulsifying substances, is chromatographically stable and amen- able to purification and chemical characterization.Õ The notion that the renal medulla secretes a blood pressure lowering hormone, Ôthe yin to angiotensin’s yangÕ, stretches back many decades. The champion of this concept, Eric Muirhead, died in 1994. Since then, there has been virtually no published account of original work aimed at extraction, isolation and chemical characterization of this putative factor. The study by Glodny and Pauli in this issue utilized state-of-the-art analytical methods to investigate the chemistry of a lipid extract from medullary tissue with depressor activity. This was clearly a mammoth task, involving at the outset extraction of lipid from 3500 porcine kidneys. Crude chloro- form extraction procedures were fol- lowed by large scale vacuum chromatography, and individual frac- tions were tested for depressor activity in anaesthetized rats. Fractions with depressor activity were then subjected to gas chromatography and mass spectrometry. The authorsÕ major finding was that vasodilator prosta- noids (A 2 ,E 2 ,F 2a I 2 ) could not be detected in the lipid fractions with depressor activity. Interestingly, the time course of the depressor response to the lipid extract bore a striking resemblance to that of Muirhead’s Ôantihypertensive neutral renomedul- lary lipidÕ (medullipin). Thus, the authors have provided the basis for isolation and chemical characteriza- tion of the putative renal medullary depressor hormone. Roger Evans Department of Physiology, Monash University, Melbourne, Australia [email protected] Guest editor Acta Physiol 2006, 187, 355 Ó 2006 Scandinavian Physiological Society, doi: 10.1111/j.1748-1716.2006.1590.x 355

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Page 1: The putative renal medullary depressor hormone: medullipin rises like Phoenix from the ashes?

Editor’s Choice

Capillary growth in response toexercise training is retained inageing human skeletal muscleand can be demonstratednon-invasively

�Microvascular filtration rate and

microvascular tortuosity changed in

like manner after exercise training in

the elderly suggesting a preserved

adaptation capacity�.

In skeletal muscles, an increase in

capillary numbers is a hallmark of

adaptation to endurance exercise

training, contributing to increased

aerobic capacity. This has been shown

in both young and elderly humans

based usually on the analysis of inva-

sively obtained muscle biopsies. The

study by Charles and colleagues in this

issue has employed a non-invasive

method of evaluating fluid filtration

rate in human lower limbs as an index

of microvascular exchange surface

area and compared it to histological

data on capillarity from quadriceps

muscle biopsy samples in elderly men

(mean age 74 years) undertaking a

14 week endurance exercise training

programme. Peak oxygen consump-

tion increased by 11%, muscle citrate

synthase activity by 28% and calf

reactive hyperaemia by 21%, con-

firming training effects. In muscle

biopsies, the length of microvessel wall

in contact with the muscle fibre peri-

meter increased 26% overall after

training, while calf microvascular fil-

tration rate determined non-invasively

by venous occlusion plethysmography

increased by 79%. Within all subjects,

the two indices correlated significantly

implying a common effect of training

on exchange surface area albeit in

different leg muscles. Increased contact

length between microvessels <15 lmdiameter and fibres in muscle cross-

sections also suggests that growth has

occurred by transverse sprouting and/

or lengthening of existing vessels.

M. D. BrownSchool of Sport and Exercise

Sciences, University ofBirmingham, Birmingham, UK

[email protected] editor

The putative renal medullarydepressor hormone: medullipinrises like Phoenix from theashes?

�The vasodepressor principle is con-

tained in the kidney medulla, but not

in the cortex. It can be separated from

endogenous emulsifying substances, is

chromatographically stable and amen-

able to purification and chemical

characterization.�

The notion that the renal medulla

secretes a blood pressure lowering

hormone, �the yin to angiotensin’s

yang�, stretches back many decades.

The champion of this concept, Eric

Muirhead, died in 1994. Since then,

there has been virtually no published

account of original work aimed at

extraction, isolation and chemical

characterization of this putative factor.

The study by Glodny and Pauli in this

issue utilized state-of-the-art analytical

methods to investigate the chemistry of

a lipid extract from medullary tissue

with depressor activity. This was

clearly a mammoth task, involving at

the outset extraction of lipid from

3500 porcine kidneys. Crude chloro-

form extraction procedures were fol-

lowed by large scale vacuum

chromatography, and individual frac-

tions were tested for depressor activity

in anaesthetized rats. Fractions with

depressor activity were then subjected

to gas chromatography and mass

spectrometry. The authors� major

finding was that vasodilator prosta-

noids (A2, E2, F2a I2) could not be

detected in the lipid fractions with

depressor activity. Interestingly, the

time course of the depressor response

to the lipid extract bore a striking

resemblance to that of Muirhead’s

�antihypertensive neutral renomedul-

lary lipid� (medullipin). Thus, the

authors have provided the basis for

isolation and chemical characteriza-

tion of the putative renal medullary

depressor hormone.

Roger EvansDepartment of Physiology,

Monash University, Melbourne,Australia

[email protected] editor

Acta Physiol 2006, 187, 355

� 2006 Scandinavian Physiological Society, doi: 10.1111/j.1748-1716.2006.1590.x 355