Effect of Calcium Antagonists on Glomerular Arterioles in Spontaneously Hypertensive Rats

Abstract

Abstract-Through the use of microanatomic techniques, we investigated the effects of treatment with some dihydropyridine-type calcium antagonists (CAs) (ie, lercanidipine, manidipine, and nicardipine) and with the nondihydropyridinetype vasodilator hydralazine on hypertension-dependent glomerular injury and on the morphology of afferent and efferent arterioles in spontaneously hypertensive rats (SHR). Fourteen-week-old male SHR and age-matched normotensive Wistar-Kyoto rats were left untreated (control groups). Four additional groups of 14-week-old SHR were treated for 12 weeks with daily oral doses of 2.5 mg/kg lercanidipine, 5 mg/kg manidipine, 3 mg/kg nicardipine, or 10 mg/kg hydralazine. These treatments decreased systolic blood pressure values to a similar extent in SHR. Signs of glomerular injury, as characterized by glomerulosclerosis, hypertrophy, and an increased number of mesangial cells, were observed in control SHR. The treatment with CAs improved glomerular morphology and decreased the number of mesangial cells. Lercanidipine and manidipine were more effective than nicardipine in countering glomerular injury.In the SHR, both afferent and efferent arterioles revealed luminal narrowing, accompanied by increased wall thickness in efferent arterioles. The dihydropyridine-type derivatives that were tested decreased the luminal narrowing of afferent arterioles. Lercanidipine and manidipine countered the luminal narrowing of efferent arterioles. Hydralazine had no effect on hypertension-dependent glomerular injury or vascular changes. The present data indicate that lercanidipine and manidipine vasodilate afferent and efferent arterioles in SHR. A vasodilatory activity on efferent arteriole, which is not induced by the majority of CAs, may represent an useful property in the treatment of hypertension complicated by renal disease.

Calcium channel blockers, postural vasoconstriction and dependent oedema in essential hypertension

“…32,40,44,47 This pharmacological profile is not universal, though: DHP CCBs, such as lercanidipine and manidipine, were recently shown to cause a similar degree of relaxation in pre-as in post-capillary renal vessels. 59 That same peculiar behaviour might also extend to the postural control of cutaneous microcirculation thus preserving more efficiently intracapillary pressures and perhaps engendering less fluid extravasation, a purely speculative hypothesis at this time.…”

A randomized comparison between lercanidipine and amlodipine for efficacy and tolerability in patients with essential hypertension

“…Experimental studies have shown that lercanidipine also has a distinct vasodilatory effect on the efferent arteriole in addition to the afferent arteriole in the kidney. 13 Thus, it was stated that lercanidipine provides a more balanced pre-and postglomerular dilation, thereby reducing intracapillary pressure. It was hypothesized that such a balanced vasodilator action could take place in other capillary beds as well, which results in decreased incidence of the edema.…”

A modern choice for patients with hypertension: the possibility of new calcium antagonist of III generation

“…Эти важнейшие особенности поз-воляют не только успешно применять лерканидипин для лечения АГ у больных с протеинурией и хронической болезнью почек (ХБП), но и воздействовать на основ-ные показатели, определяющие почечную функцию [44].…”