Effect of perindopril in rat cardiac volume overload.
The aortocaval fistula is a classic model of pure cardiac volume overload in rats. This model is characterized by dilation of the ventricular cavities and eccentric cardiac hypertrophy. There are also changes in peripheral arterial flow: high flow in the proximal part of the aorta, upstream of the shunt, and low flow in the distal aorta, downstream of the shunt. The chronic effects of converting enzyme inhibition in this model of volume overload have not yet been measured. We tested the effect of blood pressure and flow on cardiac mass and aortic dilatory pathway in normotensive Wistar and spontaneously hypertensive rats (SHR) with an aortocaval fistula. One half of the sham-operated rats and the normotensive and hypertensive rats with aortocaval fistulas were treated for 1 month with perindopril (2 mg/kg by daily gavage). Urine and plasma were collected at death, the heart was weighed, and the proximal (thoracic) and distal (abdominal) aortas were quickly removed and frozen in liquid nitrogen for measurement of cyclic guanosine monophosphate (cGMP). Blood pressure was always higher in SHR than in Wistar rats, in sham-operated rats than in those with aortocaval fistulas, and in untreated than in perindopril-treated rats. Similarly, the heart weight/body weight ratio was higher in SHR than in Wistar rats, in those with aortocaval fistulas than in sham-operated rats, and in untreated than in Wistar rats, in those with aortocaval fistulas than in sham-operated rats, and in untreated than in perindopril-treated rats. The aortocaval fistula increased the plasma atrial natriuretic factor and perindopril reduced it.(ABSTRACT TRUNCATED AT 250 WORDS)
Unit 367 INSERM, Paris, France.
J F
JF
Arnal
M
M
Philippe
I
I
Laboulandine
J B
JB
Michel
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001012:Aorta, Abdominal / Q000737:chemistry; D001013:Aorta, Thoracic / Q000737:chemistry; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000187:drug effects; D006152:Cyclic GMP / Q000032:analysis; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D020913:Perindopril; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP; D020913:Perindopril