Ramipril improves hemodynamic recovery but not microvascular response to ischemia in spontaneously hypertensive rats.
BACKGROUND
Angiotensin converting enzyme (ACE) inhibition exerts positive effects on the microvasculature of normotensive animals, although this concept is not universally accepted. Recently, ACE inhibitors have been suggested to be useful for rescue in peripheral ischemia.


METHODS
We investigated whether chronic treatment with the ACE inhibitor ramipril may have a positive impact on the defective healing response to ischemia that is typical of spontaneously hypertensive rats (SHR). Unilateral limb ischemia was induced in 20-week-old SHR by surgically removing the left femoral artery. Rats were allowed to regain consciousness and then were randomly allocated to treatment with ramipril (1 mg/kg body weight in drinking water) or vehicle for 28 days.


RESULTS
The SHR failed to develop reparative angiogenesis in response to ischemia, thus having inadequate perfusion recovery. Ramipril reduced both tail-cuff systolic blood pressure (180 +/- 7 v 207 +/- 2 mm Hg in the vehicle group at 28 days, P < .05) and intra-arterial mean blood pressure (115 +/- 6 v 135 +/- 5 mm Hg in the vehicle group, P < .05). These effects were associated with increased responsiveness to endothelium-dependent vasodilatation by acetylcholine. Treatment with ramipril did not influence muscular capillary and arteriole density but accelerated the rate of perfusion recovery, leading to complete healing within 28 days after surgery.


CONCLUSIONS
These results indicate that ACE inhibition by ramipril may be useful for the treatment of peripheral vascular complications in hypertension.
Emanueli
Costanza
C
Cardiovascular Medicine and Gene Therapy Section, National Laboratory of the National Institute of Biostructures and Biosystems, Osilo, Italy.
Salis
Maria Bonaria
MB
Stacca
Tiziana
T
Pinna
Alessandra
A
Gaspa
Leonardo
L
Spano
Alessandra
A
Madeddu
Paolo
P
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D007511:Ischemia / Q000209:etiology* / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D017257:Ramipril / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D017257:Ramipril