Enalapril can prevent vascular amplifier development in spontaneously hypertensive rats.

Abstract

Three groups of spontaneously hypertensive rats (SHR) were given enalapril (25 mg/kg/day) from 4 to 9 weeks, 4 to 14 weeks, and 14 to 20 weeks of age. The drug was stopped and observations continued for another 16-21 weeks. At selected times, we measured blood pressure, in vitro hindquarter vascular resistance properties, left ventricular weight/body weight ratio, and skeletal muscle vessel norepinephrine kinetics in treated and untreated SHR and in Wistar-Kyoto (WKY) rats. At the end of each treatment period, all cardiovascular variables were close to values of WKY rats and well below those of untreated SHR, and the norepinephrine or fractional rate constant was about 25% below those levels. After enalapril was stopped, blood pressure and left ventricular weight/body weight ratio increased in parallel to levels ranging from 30% to 50% of the normal difference between untreated SHR and WKY rats. However, in SHR treated from 4 to 9 weeks and from 4 to 14 weeks of age, hindquarter resistance properties remained close to WKY rat levels for the entire observation period of 16-21 weeks after treatment, suggesting suppression of the enhanced resistance responses of SHR (amplifier properties). In SHR treated from 14 to 20 weeks of age, suppression of amplifier properties was more transient, and they redeveloped partially 5-6 weeks after cessation of therapy. When enalapril was given up to 14 weeks of age, the long-term suppression of amplifier properties was probably mainly through prevention of smooth muscle hypertrophy in resistance vessels and possibly through other mechanisms (eg., "rarefaction"). After that age, its therapeutic action was similar to that of other antihypertenslve drugs where, after drug withdrawal, there is a slow pressure rise in parallel with redevelopment of vascular and cardiac hypertrophy. (Hypertension 1990;16:252-260)

Antihypertensive Treatment and the Responsiveness to Glutamate in Ventrolateral Medulla

“…A decrease in body weight as the result of treatment with enalapril 13,14 or other ACE inhibitors 15,16 has also been reported by other investigators. The mechanism of body weight reduction is not fully understood but may be explained in part by the natriuresis produced by ACE inhibitors, as has been suggested by Clozel et al 17 Because we did not measure sympathetic nerve activity in this study, we cannot exclude the possibility that the difference in pressor response evoked by microinjection of EAA into the RVLM may be due to the responsiveness of peripheral vessels rather than a difference in the sympathetic outflow.…”

Time Course of Vascular Structural Changes During and After Short-Term Antihypertensive Treatment

“…Although the concept is somewhat controversial, some investigators have maintained that there is a mechanistic association between regression of vascular structure and persistent reduction of MAP. 1,2,8 For example, conclusions in some studies that did not support this causal link were based on a lack of statistical significance in vascular structural changes and yet the nonsignificant changes in vascular dimensions were in the order of 8% to 21%. [12][13][14] It is important to recognize, based on the Poiseuille relationship, that the average vessel lumen diameter would only have to increase by about 4% to induce a 16% decrease in vascular resistance.…”

“…[1][2][3][4] These effects have been shown in several models of experimental hypertension, including the Prague hypertensive rat 5 and the genetically hypertensive rat, 6,7 although this is best documented in the spontaneously hypertensive rat (SHR). [1][2][3]8,9 The concept that the persistent reduction in MAP and the regression of vascular structure are linked mechanistically has also been widely discussed, although without resolution. 1-4,10 -14 Further, the vascular structural changes that persist off-treatment have been proposed to result from extended inhibition of the trophic actions of angiotensin II, 8,15,16 prolonged reduction in arterial pressure, 16 -18 or from the combined effects.…”

“…[1][2][3]8,9 The concept that the persistent reduction in MAP and the regression of vascular structure are linked mechanistically has also been widely discussed, although without resolution. 1-4,10 -14 Further, the vascular structural changes that persist off-treatment have been proposed to result from extended inhibition of the trophic actions of angiotensin II, 8,15,16 prolonged reduction in arterial pressure, 16 -18 or from the combined effects. Regardless of the mechanism of action, the result is a reduced thickness of the medial layer and an increase in the lumen size of the vessels 4,6,19 that lasts long after the cessation of therapy.…”

Effects of a beta-blocker or a converting enzyme inhibitor on resistance arteries in essential hypertension.

“…28 If the vasodilator hydralazine is given simultaneously and blood pressure does not rise, this hypertrophic response still occurs, indicating that it is at least in part independent of blood pressure. When spontaneously hypertensive rats are treated with converting enzyme inhibitors 17 ' 29 or angiotensin II antagonists, 18 vascular structure regresses partly but not entirely to normal. In a model of renin-dependent hypertension in the rat, treatment with cilazapril produced complete regression of vascular changes, 30 although this was associated with normalization of blood pressure.…”