Ethnic differences in vascular contractility and remodeling.

Previous studies have established that black people have an increased
prevalence of essential hypertension compared with white people. The disease
onset is earlier, and the consequences of hypertension, which include heart
failure, myocardial infarction, stroke, and renal failure, are more pronounced
in black patients.
One factor contributing to the development and progression of hypertension in
blacks is hemodynamic reactivity characterized by greatly increased peripheral
vascular resistance in response to external stimuli, including physical and
mental stress.
Regarding the mechanism for the increased peripheral vascular resistance in
black patients, endothelial as well as muscular factors have been proposed.
Vasoactive substances produced by endothelial cells such as endothelin-1 (ET-1)
and NO are possible candidates to contribute to the vascular reactivity.
Regarding vascular smooth muscle factors, a vast amount of energy is needed for
muscular contraction and development of hypertension. Cross bridge cycling and
ion transport are the most energy demanding process in cellular metabolism and
creatine kinase, the central regulatory enzyme of energy metabolism, serves as
the major cellular ATP regenerating system for these cellular functions.
There are large inter-individual differences in creatine kinase activity in
healthy people. In particular black people have very high skeletal muscle and
serum creatine kinase activity, to be about eighty to a hundred percent higher
than in white and other people.
We have therefore postulated that the genetic factor increasing the propensity
of black people of sub-Saharan African descent to develop high blood pressures
is relatively high activity of creatine kinase in tissue, increasing
cardiovascular contractile reserve, enhance trophic responses and increase
renal tubular ability to retain salt, facilitating the development of arterial
hypertension under chronic provocative circumstances. In vascular smooth
muscle, cGMP and cAMP dependent pathways are thought to inhibit contractility
less effective than creatine kinase or calcium inhibitors, because the effect
of creatine kinase is likely to depend on downstream targets of cyclic
nucleotides related to calcium transients and myosin ATP-ase activity.

To study etnic differences in contractillity of the smooth muscle and to
investigate the role of CK in this proces.

I. Recruitment at the outpatient department.

II. Questionnaire and blood pressure measurement.
II.1. general questions:
We will ask the patients* permission to obtain medical information from his/her
medical record and ask additional questions if necessary.

II.2. fainting specific questionnaire:
Historical data of the patient regarding to fainting will be collected
preoperatively with the help of a specific questionnaire.

II.3. Physical examination:
We will measure blood pressure with a oscillometric device one day before
surgery and six weeks thereafter. Measurements will be performed in seated
position, on the non-dominant arm at heart level.

III. Serum creatine kinase levels
CK levels in blood will be included with the standard preoperative assessment.

IV. Tissue biopsy and tissue study.
Resistance vessels will be isolated for contractility studies and histological
examination, from omental fat of black and white men and women obtained during
abdominal surgery, after informed consent is given.
The morphology will be studied with the help of ligth microscopy and electron
microscopy. A wire-myograph will be used to study noradrenalin contractility,
endothelium-dependent bradykinin relaxation, the vascular respons to calcium
blockade, NO donation and creatine kinase inhibition. Finally we will asses
tissue CK.

V. Vessel culture.
Culture of resistance vessels for 2-3 days.

Biopsies of fat are considered to be procedures with minimal risk. We have
performed this procedure in more than 40 patients at our hospital without ill
effects. There is no direct benefit for the individual, however we do expect
long-term benefits for the ethnic group participants belong to.