Abstract
Vascular changes that develop during the course of blood pressure rise in spontaneously hypertensive rats (SHRs) can be modified by antihypertensive therapy. It is not known, however, whether there is selectivity in the structural response to specific antihypertensive drugs. This issue was examined by comparing the effects of a direct vasodilator (hydralazine) and a converting enzyme inhibitor (captopril) on morphologic aspects of the cardiovascular system. Male SHRs, 21 weeks of age, were given either hydralazine (HCl plus hydrochlorothiazide, captopril plus hydrochlorothiazide, or hydrochlorothiazide alone. Untreated age-matched SHRs and Wistar-Kyoto normotensive rats (WKYs) were used as controls. Animals were sacrificed at 27-28 weeks of age. Both hydralazine and captopril lowered significantly the blood pressure of SHRs, whereas hydrochlorothiazide alone was ineffective. The heart/body weight ratios were dramatically reduced in captopril-treated SHRs to below the level of WKYs; hydralazine induced only a very modest (5%) reduction, whereas the diuretic alone was ineffective. The morphology of the aortic intima improved dramatically in response to captopril and hydralazine and, to a lesser extent, hydrochlorothiazide alone. This effect becomes apparent within 6 weeks of treatment, and the only evidence of preexisting disease is the persistence of collagen in the subendothelium. Captopril and hydralazine, but not hydrochlorothiazide alone, reduce the thickness of the aortic media below that of normotensive controls. In addition, captopril and hydralazine improve the structure of small intrarenal vessels. There was a strong correlation between the relative effectiveness of the three pharmacologic agents in lowering blood pressure and in improving the changes of intrarenal vessels. These results highlight the capacity of antihypertensive therapy to arrest or reverse the structural sequelae of hypertension. In addition, they underscore the heterogeneity in the response of different components of the cardiovascular system, which, in part, reflects selectivity in the action of antihypertensive agents.
Full text
PDF
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alderman M. H., Madhavan S. Management of the hypertensive patient: a continuing dilemma. Hypertension. 1981 Mar-Apr;3(2):192–197. doi: 10.1161/01.hyp.3.2.192. [DOI] [PubMed] [Google Scholar]
- Antonaccio M. J., Rubin B., Horovitz Z. P., Laffan R. J., Goldberg M. E., High J. P., Harris D. N., Zaidi I. Effects of chronic treatment with captopril (SQ 14,225), an orally active inhibitor of angiotensin I-converting enzyme, in spontaneously hypertensive rats. Jpn J Pharmacol. 1979 Apr;29(2):285–294. doi: 10.1254/jjp.29.285. [DOI] [PubMed] [Google Scholar]
- Blaustein M. P. Sodium ions, calcium ions, blood pressure regulation, and hypertension: a reassessment and a hypothesis. Am J Physiol. 1977 May;232(5):C165–C173. doi: 10.1152/ajpcell.1977.232.5.C165. [DOI] [PubMed] [Google Scholar]
- Cox R. H. Comparison of arterial wall mechanics in normotensive and spontaneously hypertensive rats. Am J Physiol. 1979 Aug;237(2):H159–H167. doi: 10.1152/ajpheart.1979.237.2.H159. [DOI] [PubMed] [Google Scholar]
- Danon D., Goldstein L., Marikovsky Y., Skutelsky E. Use of cationized ferritin as a label of negative charges on cell surfaces. J Ultrastruct Res. 1972 Mar;38(5):500–510. doi: 10.1016/0022-5320(72)90087-1. [DOI] [PubMed] [Google Scholar]
- Folkow B. Physiological aspects of primary hypertension. Physiol Rev. 1982 Apr;62(2):347–504. doi: 10.1152/physrev.1982.62.2.347. [DOI] [PubMed] [Google Scholar]
- Freis E. D., Ragan D. O. Relative effectiveness of chlorothiazide, reserpine and hydrallazine in spontaneously hypertensive rats. Clin Sci Mol Med Suppl. 1976 Dec;3:635s–637s. doi: 10.1042/cs051635s. [DOI] [PubMed] [Google Scholar]
- Limas C., Westrum B., Iwai J., Limas C. J. Aortic morphology in salt-dependent genetic hypertension. Am J Pathol. 1982 Jun;107(3):378–394. [PMC free article] [PubMed] [Google Scholar]
- Limas C., Westrum B., Limas C. J. Effect of antihypertensive therapy on the vascular changes of spontaneously hypertensive rats. Am J Pathol. 1983 Jun;111(3):380–393. [PMC free article] [PubMed] [Google Scholar]
- Limas C., Westrum B., Limas C. J. The evolution of vascular changes in the spontaneously hypertensive rat. Am J Pathol. 1980 Feb;98(2):357–384. [PMC free article] [PubMed] [Google Scholar]
- Luft J. H. Ruthenium red and violet. I. Chemistry, purification, methods of use for electron microscopy and mechanism of action. Anat Rec. 1971 Nov;171(3):347–368. doi: 10.1002/ar.1091710302. [DOI] [PubMed] [Google Scholar]
- Preston B. N., Snowden J. M., Houghton K. T. Model connective tissue systems: the effect of proteoglycans on the distribution of small non-electrolytes and micro-ions. Biopolymers. 1972;11(8):1645–1649. doi: 10.1002/bip.1972.360110811. [DOI] [PubMed] [Google Scholar]
- Prichard B. N., Gillam P. M., Graham B. R. Beta receptor antagonism in hypertension; comparison with the effect of adrenergic neurone inhibition on cardiovascular responses. Int Z Klin Pharmakol Ther Toxikol. 1970 Dec;4(1):131–140. [PubMed] [Google Scholar]
- Singer H. A., Peach M. J. Calcium- and endothelial-mediated vascular smooth muscle relaxation in rabbit aorta. Hypertension. 1982 May-Jun;4(3 Pt 2):19–25. [PubMed] [Google Scholar]