Invited Symposium: Hypertension I: Structure of Small Arteries in Hypertension
It has been well established that drugs that antagonize the renin-angiotensin system (RAS), such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 (AT1) receptor antagonists can induce a persistent lowering of blood pressure even after the withdrawal of treatment. These drugs have also been shown to cause a regression of vascular structure after long-term treatment. It has been suggested that there is a causal link between this structural sownregulation and the persistent lowering of blood pressure.
Six weeks of ACE inhibitor treatment induces a 20-30% reduction in structurally-based vascular resistance properties (Adams et al, 1990). The present study investigated whether the regression induced after only two weeks of RAS inhibition is proportional to the duration of treatment, i.e. one third of the regression observed after six weeks of therapy. To assess this we used an established hemodynamic technique based on the Poiseuille relationship to determine the regression of structurally-based vascular resistance at both maximum constriction and maximum dilation.
Enalapril, an ACE inhibitor, or losartan, an AT1 receptor antagonist was given to SHR in the drinking water for two weeks prior to assessment.
Materials and Methods
Treatment Groups (2 weeks)
Hearts excised, blotted dry, right ventricle and left ventricle plus septum separated and weighed
Fig. 1: Enalapril and losartan both induce a similar reduction of structurally-based vascular resistance properties (at maximum vasoconstriction) below control after 2 weeks of treatment (15%, 16% *p < .05).
Fig. 2: Enalapril and losartan both induce reduction in left ventricle to body weight ratio (18%, 12% *p < .05) below control values.
Fig. 3: Comparison of log EC50, slope of alpha1 adrenoceptor concentration-response curve, and the slope of the flow-pressure curves with the different treatments.
Discussion and Conclusion
|Hale, T.M.; Bushfield, T.L.; Adams, M.A.; (1998). Early Vascular Structural Changes After Short Term RAS Inhibition: Evidence for a Reversible Component of Regression. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/mulvany/hale0778/index.html|
|© 1998 Author(s) Hold Copyright|