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It has been proposed that an impairment of endothelial mitochondrial
oxidative phosphorylation might be the cause of many acute and chronic
diseases including thromboembolism and atherosclerosis (1,2). In these
instances it was suggested that the triggering event might be activation
by the accumulation of ADP of the ADP receptor P2Yto promote platelet
adhesion and thrombus formation in either static or flowing blood. The
hypothesis is consistent with the therapeutic benefits of platelet ADP
receptor antagonists such as ticlopidine and clopidogrel. Might an
impairment of endothelial oxidative phosphorylation also be the cause of
arterial hypertension?
People living at low altitudes who move to live at high altitude
develop pulmonary artery hypertension, as reported in a review in today's
New Scientist. The pulmonary hypertension is believed to be the product of
hypoxia. Acute arterial occlusion in an animal model induces smooth muscle
contraction in the distal vessels and in the gut followed by relaxation.
The contraction in the arterial vessels is probably a manifestation of a
neural reflex for surgical dissection of an artery has the same effect.
The contraction of the gut is not.
Acute arterial occlusion causes a tissue acidosis (3). A fall in
tissue pH increases the concentration of ionised calcium (4). This may
cause smooth muscle contraction, an effect that can be blocked by calcium
channel blockers, and stimulate the release of renin from the juxta-
glomerlular apparatus which in turn stimulates the release of angiotensin
II (5,6). Clacium may also stimulate angiotensin II release by a direct
effect upon stimulus-secretion coupling. Angiotensin II is a potent
vasoconstrictor, its selective effect upon splanchnic vasculature
accounting almost entirely for the rise in total vascular resistance it
induces (7).
It is concluded that arterial hypertension may indeed be caused by an
impairment of mitochondrial oxidative phosphorylation. The effect could be
induced by both direct and indirect actions. Hence the hypotensive effects
of both calcium channel blockers and ACE inhibitors.
1. Unreversed ATP hydrolysis: the initiating endothelial event?
Richard G Fiddian-Green
bmj.com/cgi/eletters/325/7369/887#26445, 22 Oct 2002
2. Iatrogenic diseases with a common cause?
Richard G Fiddian-Green
bmj.com/cgi/eletters/325/7370/913#26512, 25 Oct 2002
You don't mention physical activity in your article. The evidence is
there though. Physical activity, even at modest levels, both prevents and
treats hypertension. Physical activity is therefore to be integrated in
the palette of means to prevent and treat hypertension.
Sincerely,
Bengt Kayser
Competing interests:
No competing interests
28 October 2002
Bengt Kayser
Prof
Faculty of medicine, University of Geneva, 1211 Geneva 4, Switzerland,
Hypertension: product of mitochondrial dysfunction?
It has been proposed that an impairment of endothelial mitochondrial
oxidative phosphorylation might be the cause of many acute and chronic
diseases including thromboembolism and atherosclerosis (1,2). In these
instances it was suggested that the triggering event might be activation
by the accumulation of ADP of the ADP receptor P2Yto promote platelet
adhesion and thrombus formation in either static or flowing blood. The
hypothesis is consistent with the therapeutic benefits of platelet ADP
receptor antagonists such as ticlopidine and clopidogrel. Might an
impairment of endothelial oxidative phosphorylation also be the cause of
arterial hypertension?
People living at low altitudes who move to live at high altitude
develop pulmonary artery hypertension, as reported in a review in today's
New Scientist. The pulmonary hypertension is believed to be the product of
hypoxia. Acute arterial occlusion in an animal model induces smooth muscle
contraction in the distal vessels and in the gut followed by relaxation.
The contraction in the arterial vessels is probably a manifestation of a
neural reflex for surgical dissection of an artery has the same effect.
The contraction of the gut is not.
Acute arterial occlusion causes a tissue acidosis (3). A fall in
tissue pH increases the concentration of ionised calcium (4). This may
cause smooth muscle contraction, an effect that can be blocked by calcium
channel blockers, and stimulate the release of renin from the juxta-
glomerlular apparatus which in turn stimulates the release of angiotensin
II (5,6). Clacium may also stimulate angiotensin II release by a direct
effect upon stimulus-secretion coupling. Angiotensin II is a potent
vasoconstrictor, its selective effect upon splanchnic vasculature
accounting almost entirely for the rise in total vascular resistance it
induces (7).
It is concluded that arterial hypertension may indeed be caused by an
impairment of mitochondrial oxidative phosphorylation. The effect could be
induced by both direct and indirect actions. Hence the hypotensive effects
of both calcium channel blockers and ACE inhibitors.
1. Unreversed ATP hydrolysis: the initiating endothelial event?
Richard G Fiddian-Green
bmj.com/cgi/eletters/325/7369/887#26445, 22 Oct 2002
2. Iatrogenic diseases with a common cause?
Richard G Fiddian-Green
bmj.com/cgi/eletters/325/7370/913#26512, 25 Oct 2002
3. Gastric intramucosal pH, tissue oxygenation and acid-base balance.
Br J Anaesth. 1995 May;74(5):591-606. Review.
Fiddian-Green RG.
4. Dewitte K, Stockl D, Thienpont LM. pH dependency of serum ionised
calcium.
Lancet. 1999 Nov 20;354(9192):1793-4.
5. Rasmussen H. Cellular calcium metabolism.
Ann Intern Med. 1983 May;98(5 Pt 2):809-16.
6. Fray JC. Stimulus-secretion coupling of renin. Role of hemodynamic
and other factors.
Circ Res. 1980 Oct;47(4):485-92. Review.
7. Reilly PM, Bulkley GB. Vasoactive mediators and splanchnic
perfusion.
Crit Care Med. 1993 Feb;21(2 Suppl):S55-68. Review.
Competing interests:
None declared
Competing interests: No competing interests