Compared myocardial and vascular effects of captopril and dihydralazine during hypertension development in spontaneously hypertensive rats

Abstract

1 When administered to young spontaneously hypertensive rats (SHRs), dihydralazine (25 mg kg-', daily) and captopril (100mg kg-, daily) prevent with the same efficacy genetic hypertension development (GHD). 2 Dihydralazine treatment increased vascular mesenteric compliance, as shown by a significant decrease in the stiffness of the vessels (-27%), and induced slight reductions in contractility (-12%) and in wall to lumen (W/L) ratio (-15%). After treatment withdrawal, all these parameters returned to control values within 7 weeks, as did blood pressure. 3 Captopril treatment also strongly increased the mesenteric vessels compliance, vessel stiffness being decreased by 16%, and reduced their contractility (-15%) and their W/L ratio (-30%). These effects as well as those exerted on blood pressure persisted up to 7 weeks after treatment ceased although there was a slight trend to a progressive reduction in the intensity of both phenomena. 4 These experiments show that captopril but not dihydralazine has a long-lasting effect in opposing the functional and morphological vascular alterations occurring during GHD in SHRs and this phenomenon probably contributes to a large extent to the sustained preventive effects of the drug against GHD.

Prevention and regression of hypertension: role of renal microvascular protection

“…In this simple experiment, the arteriolar hypertrophy was found to be significantly reduced in the ARB-treated rats compared with the CCB-treated rats, despite similar reductions in blood pressure ( Figure 2). Similar results have been reported by other groups using ACE inhibitors in both animal models, 16,62 and humans. 63,64 We also examined renal arteriolar structure in rats treated with highdose 'pulse' ARB therapy, and found a remarkable reversal of the arteriolar hypertrophy found in SHR treated with ARB, whereas this effect was not seen with CCB ( Figure 3).…”

Kinetics of cardiac and vascular remodeling by spontaneously hypertensive rats after discontinuation of long-term captopril treatment

“…These findings differ from those obtained with other antihypertensive drugs administered to SHR such as β-blockers, vasodilators and calcium antagonists, whose discontinuation results in a return of blood pressure levels www.bjournal.com.br Braz J Med Biol Res 43(4) 2010 equivalent to those seen in untreated animals (13,14). Freslon and Giudicelli (12), for example, observed that treatment with captopril and hydralazine normalized blood pressure. However, only the animals treated with captopril (100 mg·kg -1 ·day -1 ) maintained normal blood pressure levels for 7 weeks after treatment interruption.…”

“…Some studies have shown that the long-term use of captopril in SHR in the prehypertensive phase is able not only to prevent the development of high blood pressure levels and cardiac hypertrophy, but also to maintain low blood pressure levels even after discontinuation of its use (2,12). These findings differ from those obtained with other antihypertensive drugs administered to SHR such as β-blockers, vasodilators and calcium antagonists, whose discontinuation results in a return of blood pressure levels www.bjournal.com.br Braz J Med Biol Res 43(4) 2010 equivalent to those seen in untreated animals (13,14).…”

The effect of enalapril on baroreceptor mediated reflex function in normotensive subjects.

“…A number of arguments could have contributed to ACEIs-induced BRS alteration: (a) ACEIs eliminate angiotensin II vasoconstrictor effects, modify vasomotor tone, as shown in our experiments by a reduction in phenylephrine pressuretime product and an augmentation in nitroglycerin pressure-time product, and increase arterial compliance (Freslon & Giudicelli, 1983;Ibsen etal., 1983;Simon etal., 1983Simon etal., , 1984 which might have led to an increased baroreceptors firing rate (Randall et al, 1978;Mancia et al, 1982) on the afferent portion of the BR; (b) angiotensin II stimulates receptors in the area postrema inducing an increase in blood pressure and antagonizing centrally the BR (Ferrario et al, 1979;Hatton et al, 1981). Hence, ACEIs by preventing angiotensin II formation could have induced the opposite effects, i.e.…”