Effects of angiotensin converting enzyme inhibition on endothelium-dependent vasodilatation in essential hypertensive patients.
BACKGROUND
Essential hypertension is characterized by an impairment of endothelium-dependent vasodilatation.


OBJECTIVE
To test whether antihypertensive treatment with the angiotensin converting enzyme inhibitor lisinopril can improve vasodilatation in response to endothelium-dependent agonists in essential hypertensive patients.


METHODS
We studied the effect of acute (6-8 h after dosing), prolonged (1 month) and chronic (12 months) lisinopril treatment on forearm blood flow response (strain-gauge plethysmography) induced in 10 hypertensive patients (aged 43.6 +/- 8.1 years, blood pressure 151.4 +/- 6.8/99.8 +/- 3.3 mmHg) by intrabrachial infusions of 0.15, 0.45, 1.5, 4.5, and 15 microg/100 ml per min acetylcholine and 5, 15, and 50 ng/100 ml per min bradykinin, two endothelium-dependent vasodilators, and 1, 2, and 4 microg/100 ml per min sodium nitroprusside, an endothelium-independent vasodilator. At baseline, vascular response was compared with that of 10 normotensive subjects (aged 42.4 +/- 6.6 years, blood pressure 118.4 +/- 6.1/77.8 +/- 3.4 mmHg).


RESULTS
Hypertensive patients had blunted (P < 0.01 or less) vasodilatations in response to infusions of acetylcholine (from 3.7 +/- 0.3 to 18.3 +/- 4.9 ml/100 ml per min) and bradykinin (from 3.7 +/- 0.4 to 15.8 +/- 2.6 ml/100 ml per min) compared with those of controls (from 3.6 +/- 0.3 to 25.3 +/- 5.2 ml/100 ml per min for acetylcholine and from 3.7 +/- 0.3 to 26.9 +/- 4.9 ml/100 ml per min for bradykinin) whereas the responses to infusion of sodium nitroprusside were similar (from 3.6 +/- 0.3 to 18.5 +/- 3.9 and from 3.6 +/- 0.3 to 16.4 +/- 1.8 ml/100 ml per min, respectively). Acute and prolonged lisinopril treatments significantly (P < 0.05 or less) improved vasodilatation in response to infusion of bradykinin (from 3.7 +/- 0.4 to 24.5 +/- 4.9 and from 3.7 +/- 0.3 to 22.1 +/- 4.9 ml/100 ml per min, respectively), but not in response to infusions of acetylcholine and of sodium nitroprusside. Chronic lisinopril treatment increased (P < 0.05) the response to infusions of not only bradykinin (from 3.5 +/- 0.5 to 27.6 +/- 5.3 ml/100 ml per min), but also of acetylcholine (from 3.5 +/- 0.5 to 27.8 +/- 8.0 ml/100 ml per min) and sodium nitroprusside (from 3.4 +/- 0.6 to 25.9 +/- 8.5 ml/100 ml per min). However, when the responses to infusions of acetylcholine and bradykinin were normalized with respect to that to infusion of sodium nitroprusside, only the vasodilatation in response to infusion of bradykinin was shown to have been increased by lisinopril treatment.


CONCLUSIONS
Administration of lisinopril to patients with essential hypertension can selectively increase vasodilatation in response to infusion of bradykinin.
Taddei
S
S
I Clinica Medica, University of Pisa, Italy. s.taddei@int.med.unipi.it
Virdis
A
A
Ghiadoni
L
L
Mattei
P
P
Salvetti
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D001920:Bradykinin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D017706:Lisinopril / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D014665:Vasodilator Agents; D017706:Lisinopril; D000109:Acetylcholine; D001920:Bradykinin