Local microvascular reactivity to Acetylcholine in patients with essential hypertension: possible interactions with the local renin-angiotensin system.

In a pilot study (MEC 02-188) we investigated the effect of topically
administrated Angiotensin II (0,01 %) on the microcirculation of the bulbar
conjunctiva in hypertensive patients. We found that the average decrease in
arteriolar diameter after Angiotensin II (Ang II) eye drops in normotensive
(control) group was larger as compared to the hypertensive group. These results
are in contrast with animal studies, where Ang II administration in
hypertensive animals, leads to a larger blood pressure response and an
increased vasoconstriction.
A possible explanation for the diminished vasoconstrictor effect of Ang II in
hypertension, is the simultaneous stimulation of endogenic nitric oxide (NO)
production, to counteract the effect of Ang II. Several studies have shown that
the vasoconstrictor effect of Ang II is partially counterbalanced by the
simultaneously stimulation of endogenous NO production, possible via activation
of the AT2-receptor. Such an effect may vary between different vascular beds,
due to different expression levels of the AT2-receptor.

We aim to study the vasoactive effects of Acetylcholine (NO dependent) in
hypertensive patients and normotensive participants. Second, the correlation
between the vasoreactivity of Acetylcholine and Angiotensin II will be studied.
Third, the magnitude of vasoreactivity between the microvascular beds of the
bulbar conjunctiva and the finger skin will be compared.

After a high sodium diet of 7 days (in order to suppress the activity of the
endogenous renin-angiotensin system).
Participants will visit the University Hospital Maastricht, on two occasions,
in the morning following an overnight fast. At the start, height, weight and
blood pressure (triple) will be measured, and a venflon will be introduced into
the antecubital vein for blood sampling (to determine Ang II levels).
Participants will be studied in a quiet temperature-controlled room. The
following aspects will take place:
The microvascular effect of Acetylcholine, Sodium Nitroprusside (control), and
placebo (NaCl, 0.9%) will be studied on the morning of day 1 in the vascular
bed of the bulbar conjunctiva (using a custom build intravital microscope) and
the finger skin (using laser Doppler fluxmetry combined with iontophoresis).

At the morning of day 2, the microvascular effect of Angiotensin II and placebo
(NaCl, 0.9%) will be studied in the vascular bed of the bulbar conjunctiva and
the finger skin.

Local application of Acetylcholine, Sodium Nitroprusside, Angiotensin II and
placebo in the bulbar conjunctiva (eye drops) and the finger skin
(iontophoresis).

-Withdrawal of blood pressure lowering medication can lead to complaints and/or
unacceptable blood pressure rise (180/120 mmHg). When withdrawal of medication
leads to complaints and/or unacceptable blood pressure rise, medication will be
started again and participation in the study will be stopped. This in
consultation with the patient and the physician.
-The used dose of Acetylcholine, Sodium nitroprusside and Angiotensine II is
very low, but in very rare cases there can be an allergic reaction.
-The Microcirculation measurements used are non-invasive, the risks for the
patients are therefore very small.
- The placement of a venflon can be painful and removing it can cause bruises.