Acute changes in the renin-angiotensin system modify bradykinin and angiotensin reactivity and metabolism in conscious rats.
We have shown that angiotensin I (AI) conversion as well as bradykinin (BK) inactivation and reactivity are altered in chronic renal hypertensive rats. In the present experiments we tested the possibility that acute renal hypertension or AI and AII infusion cause alterations in both systems. Pulmonary inactivation of BK was estimated by comparing intravenous and intraaortic equipressor doses (20 mm Hg), and the extent of AI conversion was assessed by determining the equipressor doses of AI and AII that produced a 20 mm Hg rise in mean arterial pressure (MAP). Acute renal hypertension was produced by unclamping the renal pedicle (URP) occluded for 5 hours in conscious rats. Before URP, the MAP was already increased (131 +/- 2 mm Hg) and captopril (10 mg/kg, i.v.) produced a fall of 27 +/- 8 mm Hg, suggesting that the renin-angiotensin system was overactive. After URP, MAP rose to 151 +/- 3 mm Hg, and captopril completely abolished the hypertension. Before URP, reactivity to BK was increased [doses 6 times smaller than control (C), 34 +/- 5 ng], and URP produced no further elevation. Pulmonary BK inactivation (97.5% +/- 4%) was the same before and after URP. Before URP, doses of AII 5 times greater than C (2 +/- 4 pmol) were necessary, and hyporeactivity to AII was markedly increased after URP (doses 300 times larger than C). After URP, the conversion was maximal (104% +/- 2% vs 49% +/- 3% in C), and it was already elevated before URP (82% +/- 10%) when six of the nine rats studied had maximal extent of conversion.(ABSTRACT TRUNCATED AT 250 WORDS)
D000208:Acute Disease; D000803:Angiotensin I / Q000008:administration & dosage / Q000378:metabolism*; D000804:Angiotensin II / Q000008:administration & dosage; D000809:Angiotensins / Q000378:metabolism*; D000818:Animals; D001920:Bradykinin / Q000378:metabolism*; D005260:Female; D006977:Hypertension, Renal / Q000378:metabolism / Q000503:physiopathology*; D008168:Lung / Q000378:metabolism; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System
D000809:Angiotensins; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin