Arterial responses in vitro and plasma digoxin immunoreactivity after losartan and enalapril treatments in experimental hypertension

Treatment with the angiotensin-converting enzyme inhibitor, quinapril, has been shown to normalize increased dihydropyridine sensitivity and impaired potassium relaxation, characteristic features of arterial smooth muscle in spontaneously hypertensive rats, and also reduce the concentration of plasm a digoxin-like immunoreactivity in these animals. However, whether angioten sin II receptor blocker therapy can beneficially influence these variables is not known. Therefore, we compared the effects of 10-week losartan and en alapril treatments (15 and 4 mg/kd/day, respectively) on functional respons es of mesenteric arterial rings in spontaneously hypertensive rats and Wist ar-Kyoto rats. Both losartan and enalapril normalized blood pressure, cardi ac mass, and media to lumen ratio without significantly changing the media cross-sectional area in the mesenteric artery of spontaneously hypertensive rats (i.e. induced outward remodelling). The inhibitory effect of the calc ium entry blocker nifedipine on calcium-evoked contractions was similar and less marked in arterial preparations from Wistar-Kyoto rats and losartan- and enalapril-treated spontaneously hypertensive rats than in those from un treated spontaneously hypertensive rats. Furthermore, the relaxations of ar terial rings induced by the return of potassium to the organ bath (upon pre contractions elicited by potassium-free solution) were used to evaluate the function of vascular Na+,K+-ATPase. The rate of potassium relaxation was f aster in losartan- and enalapril-treated spontaneously hypertensive rats an d all Wistar-Kyoto groups than in untreated spontaneously hypertensive rats , and the response was effectively inhibited by the sodium pump inhibitor o uabain. Both treatments especially augmented the ouabain-sensitive part of the potassium-relaxation in spontaneously hypertensive rats, indicating the involvement of the sodium pump in this response. However, no significant c hanges in plasma digoxin-like immunoreactivity were observed. In conclusion , the outward remodelling following long-term AT(1)-receptor blockade and a ngiotensin-converting enzyme inhibition in spontaneously hypertensive rats was associated with normalization of the increased dihydropyridine sensitiv ity of arteries. Both losartan and enalapril treatments also augmented arte rial potassium relaxation in spontaneously hypertensive rats, suggesting en hanced function of Na+,K+-ATPase, but this effect could nor be attributed t o changes in circulating sodium pump inhibitor concentration.