ACE inhibitors inhibit muscle loss.............

[MS]

AT least in older women with hypertension.

ACE inhibitors may reduce muscle loss

David Spurgeon Quebec

Angiotensin converting enzyme (ACE) inhibitors, when taken regularly, show promise for delaying muscle loss and
disability, report researchers at Wake Forest University Baptist Medical Center, Winston Salem, North Carolina, who
studied 641 older women with hypertension (Lancet 2002;359:926-30).

Participants who took the drug continually had a significantly lower average decline in muscle strength over three years,
compared with continual, intermittent users of other antihypertensive drugs and participants who took no
antihypertensives. The average decline in walking speed over three years was 10 times lower in users of the ACE inhibitor than in the other groups.

Lead researcher Graziano Onder said: "The effect needs to be confirmed by additional research, but it points to the possibility of ACE inhibitors being used as a first
line treatment for hypertension in older adults. Currently these drugs are recommended only in certain situations." Onder and colleagues plan to extend their research
to older men.

The researchers analysed data from the women’s health and ageing study, started in 1991 by the National Institute on Ageing through a contract with Johns Hopkins
University School of Medicine. The study’s purpose was to understand the causes and course of disability in older women who are already moderately disabled but
not severely impaired.

Dr Richard Havlik, chief of the institute’s laboratory of epidemiology, demography, and biometry, called the Wake Forest study’s results "exciting." If replicated,
they could lead to "a valuable intervention."

The study measured women’s muscle strength by having them sit in a chair, extend their knees, and push as hard as they could against a device that measured force.
Walking speed was measured by having the women walk a distance of four metres.

ACE inhibitors help reduce hypertension by blocking a protein that constricts blood vessels. One theory is that the drugs improve muscle efficiency by changing a
protein in muscle cells that makes the muscles more resistant to fatigue, increasing blood flow and reducing inflammation and consequent wasting of muscle.

 

[wilson6]

MS,

Check out:

Gordon et al. ANG II is required for optimal overload-induced skeletal muscle hypertrophy. Am J Physiol Endocrin Metab 280: 150-159, 2001.

I have to look at the Lancet study. There are too many confounding variables to suggest that ACE inhibitors per se may slow muscle strength loss. The above animal study would suggest otherwise. It could be that the reduction in hypertension in these women has simply preserved better cardiovascular function and allowed them to be more active, thus they remain more fit. Which is first here, the horse or the carriage?

W6

 

[MS]

Yeah, I've taken in that study. In the light of the above Lancet study, as well as research such as below, it makes me wonder, once again, about the risks of interpreting animal studies to liberally to their application in humans. But I agree, more research is needed (preferably in non-hypertensive individuals) to clarify the issue:


Lancet. 1999 May 29;353(9167):1884-5.

Angiotensin-converting-enzyme gene insertion/deletion polymorphism and response to physical
training.


BACKGROUND: The function of local renin-angiotensin systems in skeletal muscle and adipose tissue remains largely unknown. A
polymorphism of the human angiotensin converting enzyme (ACE) gene has been identified in which the insertion (I) rather than
deletion (D) allele is associated with lower ACE activity in body tissues and increased response to some aspects of physical training.
We studied the association between the ACE gene insertion or deletion polymorphism and changes in body composition related to an
intensive exercise programme, to investigate the metabolic effects of local human renin-angiotensin systems. METHODS: We used
three independent methods (bioimpedance, multiple skinfold-thickness assessment of whole-body composition, magnetic resonance
imaging of the mid-thigh) to study changes in body composition in young male army recruits over 10 weeks of intensive physical
training. FINDINGS: Participants with the II genotype had a greater anabolic response than those with one or more D alleles for fat
mass (0.55 vs -0.20 kg, p=0.04 by bioimpedance) and non-fat mass (1.31 vs -0.15 kg, p=0.01 by bioimpedance). Changes in body
morphology with training measured by the other methods were also dependent on genotype. INTERPRETATION: II genotype, as a
marker of low ACE activity in body tissues, may conserve a positive energy balance during rigorous training, which suggests enhanced
metabolic efficiency. This finding may explain some of the survival and functional benefits of therapy with ACE inhibitors.


And

Exp Physiol 2000 Sep;85(5):575-9

Angiotensin-converting enzyme genotype affects the response of human skeletal muscle to functional
overload.

The response to strength training varies widely between individuals and is considerably influenced by genetic variables, which until now,
have remained unidentified. The deletion (D), rather than the insertion (I), variant of the human angiotensin-converting enzyme (ACE)
genotype is an important factor in the hypertrophic response of cardiac muscle to exercise and could also be involved in skeletal
muscle hypertrophy - an important factor in the response to functional overload. Subjects were 33 healthy male volunteers with no
experience of strength training. We examined the effect of ACE genotype upon changes in strength of quadriceps muscles in response
to 9 weeks of specific strength training (isometric or dynamic). There was a significant interaction between ACE genotype and
isometric training with greater strength gains shown by subjects with the D allele (mean +/- S.E.M.: II, 9.0+/-1.7 %; ID, 17.6 +/-2.2
%; DD, 14.9+/-1.3 %, ANOVA, P 0.05). A consistent genotype and training interaction (ID DD II) was observed across all of the
strength measures, and both types of training. ACE genotype is the first genetic factor to be identified in the response of skeletal muscle
to strength training. The association of the ACE I/D polymorphism with the responses of cardiac and skeletal muscle to functional
overload indicates that they may share a common mechanism. These findings suggest a novel mechanism, involving the
renin-angiotensin system, in the response of skeletal muscle to functional overload and may have implications for the management of
conditions such as muscle wasting disorders, prolonged bed rest, ageing and rehabilitation, where muscle weakness may limit function.