LONG-TERM LOW-DOSE ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR TREATMENT INCREASES VASCULAR CYCLIC GUANOSINE 3',5'-MONOPHOSPHATE

We investigated functional changes in aortic preparations of spontaneo usly hypertensive rats treated in utero and subsequently up to 20 week s of age with the angiotensin converting enzyme (ACE) inhibitors ramip ril (0.01 and 1 mg/kg per day) and perindopril (0.01 mg/kg per day). E arly-onset treatment with the high dose of ramipril inhibited aortic A CE activity, prevented the development of hypertension, increased aort ic vasodilator responses to acetylcholine (10(-8) to 10(-6) mol/L), de creased vasoconstrictor responses to norepinephrine (10(-8) mol/L), an d increased aortic cyclic GMP content by 160%. Low-dose ramipril inhib ited aortic ACE activity and attenuated the aortic vasoconstrictor res ponse to norepinephrine but had no effect on blood pressure. Low-dose treatment with ramipril and perindopril resulted in a significant incr ease in aortic cyclic GMP content by 98% and 77%, respectively. Long-t erm coadministration of the bradykinin B2-receptor antagonist Hoe 140 abolished the ACE inhibitor-induced increase in aortic cyclic GMP. Our data demonstrate that long-term treatment with ACE inhibitors can alt er vascular function of compliance vessels independently of the antihy pertensive action. The increase in aortic cyclic GMP was due to bradyk inin potentiating the action of the ACE inhibitors.