Angiotensin converting activity assessed in vivo is increased in hereditary hypertensive rats.
1. The angiotensin converting enzyme (ACE) activity of spontaneously hypertensive (SHR) and spontaneously hypertensive stroke-prone (SHRSP) rats was compared to the ACE activity of normotensive Wistar-Kyoto rats (WKY). 2. ACE activity was assessed indirectly in conscious unrestrained rats using the equipressor response end point to simultaneously calculate the extent of conversion of angiotensin I (AI) to angiotensin II (AII) and the pulmonary degradation of bradykinin (BK). 3. The pulmonary degradation of BK was significantly elevated (99.4%) in SHR rats whereas the elevation was not significant in SHRSP rats (99.2%) compared to WKY rats, even though the pulmonary inactivation of BK in WKY rats was higher (98.6%) than in normotensive Wistar rats (95.6% and 97.5%) previously studied. 4. Blood pressure responsiveness to intra-aortically injected BK (bolus injection and infusion) was markedly increased in SHR and SHRSP rats with no change in reactivity to sodium nitroprusside. 5. Conversion of AI to AII assessed by the equipressor doses of the hormones which produced a 20-mmHg rise in blood pressure was markedly elevated in SHR (86 +/- 4%) and SHRSP (80 +/- 7%) rats when compared to WKY rats (38 +/- 4%). 6. The marked increase in conversion of AI to AII in hypertensive animals, accompanied by an increased pulmonary degradation of BK in SHR rats, suggests that ACE activity is increased in conscious SHR and SHRSP rats and may participate in the genesis of hypertension in this model of genetic hypertension.
Krieger
E M
EM
Section on Biochemical Pharmacology, National Heart, Lung and Blood Institute, National Institute of Health, Bethesda, MD 20892.
Yamori
Y
Y
Lovenberg
W M
WM
D000803:Angiotensin I / Q000008:administration & dosage / Q000378:metabolism; D000804:Angiotensin II / Q000008:administration & dosage / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage / Q000378:metabolism; D002561:Cerebrovascular Disorders / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D008168:Lung / Q000201:enzymology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D011921:Rats, Inbred WKY
D000804:Angiotensin II; D009599:Nitroprusside; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin