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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vivo antiatherogenic activity of the calcium antagonist lercanidipine and its (R)-enantiomer was investigated in two different types of atherosclerotic lesions (hyperplastic and fatty-streak lesions) in rabbits. Lercanidipine (0.3, 1, and 3 mg kg(-1) week(-1)) as well as its (R)-enantiomer at 3 mg kg(-1) week(-1) were given by subcutaneous injection for 10 weeks to White New Zealand rabbits, with cholesterol feeding beginning at week 2. The hyperplastic lesion was obtained by positioning a hollow silastic collar around one carotid artery, while aortic fatty streak lesions were induced by cholesterol feeding. In untreated animals (n=5), 14 days after collar positioning an intimal hyperplasia was clearly detectable: the arteries without collar showed a intima/media (I/M) ratio of 0.03+/-0.02, whereas in carotids with a collar the ratio was 2+/-0.42. In lercanidipine-treated animals a significant and dose-dependent effect on intimal hyperplasia was observed. I/M ratios were 0.73+/-0.4, 0.42+/-0.1, 0.32+/-0.1 for 0.3, 1, and 3 mg kg(-1) week(-1), respectively (P<0.05). The lercanidipine enantiomer (3 mg kg(-1) week(-1)) was as effective as the racemate (0.41+/-0.11). Proliferation of smooth muscle cells, assessed by incorporation of BrdU into DNA, was reduced by about 50%, 70%, 85%, and 80% by lercanidipine (0.3, 1, and 3 mg kg(-1) week(-1)) and its (R)-enantiomer, respectively. The area of fatty-streaks in the aorta (n = 11-15) was significantly reduced by lercanidipine (3 mg kg(-1) week(-1), 16% vs 27%, P<0.05), a trend was observed also with lower doses. When different segments of the aorta were considered (arch, thoracic, abdominal) a significant and dose-dependent effect in the thoracic and abdominal aorta was observed also at lower doses. The (R)-enantiomer was as effective as lercanidipine. These results suggest a direct antiatherosclerotic effect of lercanidipine, independent of modulation of risk factors such as hypercholesterolemia and/or hypertension as demonstrated by the absence of stereoselectivity.
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PMID:Effect of lercanidipine and its (R)-enantiomer on atherosclerotic lesions induced in hypercholesterolemic rabbits. 988 75

Lercanidipine (Zanidip) is a new calcium antagonist belonging to the dihydropyridine family suitable for the first-line treatment of hypertension. This molecule displays a high specificity and selectivity for vascular smooth muscle cells and has, in spite of a short plasma half-life, a long duration of action due to its liposolubility. The usual and once a day dose to treat high blood pressure of any grade is 10 mg, which if needed could be increased to 20 mg once a day. It has a gradual onset of effect on blood pressure, thus leading to a good tolerability and hopefully a better compliance in the treatment of hypertension. No adaptation of the dose is needed in older patients or in patients with moderate renal or liver impairment.
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PMID:[Pharma-clinics. Drug of the month. Lercanidipine (Zanidip)]. 1060 21

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 nondihydropyridine-type 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.
Hypertension 2000 Mar
PMID:Effect of calcium antagonists on glomerular arterioles in spontaneously hypertensive rats. 1072 May 94

Hypertension is the main cause of stroke that represents the second most common cause of death in the industrialized world and a leading cause of inability of the elderly. Lowering blood pressure reduces cerebrovascular morbidity and mortality, but it is still controversial if blood pressure should be lowered in elderly individuals with concomitant cerebrovascular disease. The present study has analyzed comparatively the effect of treatment with the dihydropyridine-type Ca(2+) channel blockers lercanidipine, manidipine and nimodipine and with the non dihydropyridine-type vasodilator hydralazine on hypertension-dependent cerebrovascular changes in spontaneously hypertensive rats (SHR). Analysis included medium and small sized pial arteries and intracerebral arteries of frontal cortex, hippocampus, striatum, and cerebellum. In control SHR, systolic pressure (SBP) values were significantly higher in comparison with WKY rats. Pharmacological treatment significantly decreased SBP values, with nimodipine reducing only moderately SBP. In control SHR, thickening of arterial wall accompanied by luminal narrowing with consequent increase of the wall-to-lumen ratio occurred both in pial and intracerebral arteries. Dihydropyridine-type Ca(2+) antagonists and to a lesser extent hydralazine countered these morphological alterations. Lercanidipine displayed a particular activity on small sized intraparenchymal brain arteries, where it was more effective than other compounds tested. This activity of lercanidipine on small-sized intracerebral arteries might represent an interesting property for the treatment of hypertensive brain damage with concomitant ischemia.
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PMID:Influence of treatment with Ca(2+) antagonists on cerebral vasculature of spontaneously hypertensive rats. 1133 9

If hypertension in patients with diabetes mellitus type II is not adequately controlled by angiotensin-converting enzyme inhibitors (ACE-i), a beta-blocker is frequently added as second-line therapy. Recently, large randomized trials demonstrated the beneficial effect of second-generation dihydropyridine calcium-channel blockers in these patients. These compounds are increasingly being used to replace beta-blockers. Withdrawal of beta-blockers may influence diabetic control and may cause rebound hypertension. Any rebound hypertension from beta-blocker withdrawal may not occur if the beta-blocker is replaced with a calcium-channel blocker. A calcium-channel blocker will influence vascular resistance (VR) and blood pressure differently than a beta-blocker. Thirty-four patients with diabetes mellitus type II and a resting diastolic blood pressure above 90 mm Hg despite enalapril 10 mg daily (or equipotent dosages of other ACE-i) for at least 3 months were treated in an open label sequential comparison with the same ACE-i in combination with the beta-blocker metoprolol 100 mg for 3 months, and, subsequently for 3 more months with the same ACE-i in combination with the dihydropyridine calcium-channel blocker lercanidipine 10 mg once daily. After 6 weeks, patients with a diastolic blood pressure above 90 mm Hg were titrated up to 200 mg metoprolol or 20 mg lercanidipine once daily. Patients were examined every 6 weeks during the trial, and after 2 weeks while receiving lercanidipine. In addition to blood pressure measurements, VR was measured by iridium strain gauge plethysmography and expressed in units (1 unit = 1 mm Hg/mL blood/100 mL tissue per minute). Two of 34 patients did not complete the protocol because of non-compliance with the lercanidipine treatment in the first 2 weeks of treatment. Their data are included in the analysis. No rebound hypertension 14 days after the change-over of therapies was observed. (Mean arterial pressures [MAPs] were not significantly different from the point of withdrawal of the beta-blockers.) However, heart rate rose from 69+/-7 to 94+/-10 beats/min (p < 0.001). After 3 months on lercanidipine, MAP fell by 6+/-10 mm Hg (p = 0.002) compared to the point of withdrawal of the beta-blocker. Vascular resistance fell by 6.28+/-11.91 units (p<0.01), while glucosylated hemoglobin (HbA1c) rose by 0.4+/-0.5% (p<0.001) and body weight rose by 0.6+/-0.6 kg (p < 0.01). Multiple regression analysis revealed significant associations between decrease in VR, increase in HbAlc, and decrease in MAP, and partial dependence of these variables on one another. In hypertensive patients with diabetes type II, replacement of ACE-i and metoprolol with ACE-i and lercanidipine does not appreciably influence metabolic control and does not cause rebound hypertension. Lercanidipine was more effective than metoprolol as a second-line antihypertensive drug in these patients. At least two mechanisms may be involved: withdrawal of a pressor effect from the beta-blocker, and calcium-channel-mediated vasodilation.
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PMID:Diabetics with hypertension not controlled with ACE inhibitors: alternate therapies. 1151 86

The effects of hypertension and of treatment with dihydropyridine-type Ca2+ antagonists and the vasodilator hydralazine on renal arterial tree were investigated in spontaneously hypertensive rats (SHR) with quantitative microanatomical techniques. Pharmacological treatment decreased to a similar extent systolic blood pressure values in SHR. Increased thickness of the tunica media of intrarenal arteries accompanied and luminal narrowing were observed in control SHR. Lercanidipine, manidipine, and nicardipine significantly countered wall thickening and luminal narrowing. Hydralazine countered luminal narrowing only. Dihydropyridines exerted renal vasocilatory activity primarily on resistance arteries, being lercanidipine the only compound active on small sized arteries.
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PMID:Effects of dihydropyridine-type Ca2+ antagonists on the renal arterial tree in spontaneously hypertensive rats. 1174 26

Calcium-channel blockers (CCBs) have been used for the treatment of hypertension for more than 20 years, and recent clinical trials support the efficacy and safety of long-acting dihydropyridine (DHP) CCBs for a wide spectrum of hypertensive patients, including diabetic hypertensive patients. DHP CCBs are effective agents overall and are particularly effective when used in combination with other agents. Lercanidipine is a novel DHP CCB effective for the treatment of mild-to-moderate hypertension. Compared with other DHP CCBs, lercanidipine has a molecular design that imparts greater solubility within the arterial cellular membrane bilayer, membrane-controlled kinetics, and a high cholesterol tolerance factor. These favorable membrane-controlled kinetics impart a gradual onset of vasodilation and a long duration of action. Further, the unique pharmacokinetic and pharmacodynamic properties of lercanidipine appear to contribute to its efficacy and favorable safety profile. In clinical trials in the treatment of mild-to-moderate hypertension, lercanidipine was administered at a starting dose of 10 mg once daily, and increased to 20 mg once daily for nonresponders. Studies have shown that lercanidipine has a 24-hour antihypertensive effect and causes no significant increase in heart rate. Lercanidipine has been shown to be effective in a wide range of hypertensive patients, including mild-to-moderate hypertension, severe hypertension, the elderly, and those with isolated systolic hypertension. It is associated with a low rate of adverse events. Because of its efficacy and favorable safety profile, lercanidipine has the potential to improve blood pressure control in a wide range of patients, including those who have not responded to, or who have been unable to tolerate, other antihypertensive agents.
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PMID:Lercanidipine: a novel dihydropyridine calcium-channel blocker. 1197 24

Hypertension, by definition, is a hemodynamic disorder. A high cardiac output and a normal systemic vascular resistance characterize the young hypertensive patient. As hypertension progresses, resistance becomes progressively elevated and cardiac output returns to normal. The elderly patient with hypertension has very high systemic vascular resistance and low cardiac output. Antihypertensive drugs should not only lower arterial pressure but also bring other hemodynamic parameters as well as functional and structural changes of the cardiovascular system back to normal. With the notable exception of the classic beta-blockers, all antihypertensive drug classes, including the vasodilating beta-blockers, increase or maintain cardiac output and lower systemic vascular resistance. Calcium antagonists, although a very heterogeneous group, have been shown to have a similar effect on systemic hemodynamics. Initially, the short-acting agents (even verapamil) produce a reflex increase in heart rate and cardiac output with a decrease in systemic vascular resistance. This reflexive cardiac acceleration is not seen with the extended-release or longer-acting formulations, which usually maintain cardiac output and decrease systemic resistance. Lercanidipine is a novel calcium antagonist that has been shown to differ from other dihydropyridines in that the incidence of vasodilatory edema for any given decrease in blood pressure is less pronounced. Whereas all dihydropyridine calcium antagonists dilate the afferent arteriole in the kidney, preclinical studies have shown that lercanidipine also produces dilation of the efferent vessel. Similar balanced pre- and postcapillary vasodilation may be an explanation for the lower incidence of vasodilatory edema seen clinically with lercanidipine. These micro- and macrovascular features make lercanidipine an attractive new member in the arsenal of the powerful dihydropyridine calcium antagonists.
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PMID:Calcium antagonists in hypertension: from hemodynamics to outcomes. 1212 Oct 12

Essential hypertension is associated with impaired endothelium-dependent vasodilation caused by oxidative stress-induced nitric oxide (NO) breakdown and compensatory production of a hyperpolarizing factor. To test whether calcium antagonist treatment can restore NO availability and prevent hyperpolarization through antioxidant properties, in 15 healthy subjects and 15 patients with essential hypertension, we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial bradykinin (5, 15, 50 ng/100 mL per minute), an endothelium-dependent vasodilator, in basal conditions, during infusion of NG-monomethyl-l-arginine (L-NMMA, 100 microg/100 mL per minute), an NO-synthase inhibitor, and ouabain (0.72 microg/100 mL per minute), an Na+-K+ ATPase inhibitor to prevent hyperpolarization. These infusions were repeated in the presence of the antioxidant vitamin C (8 mg/100 mL/min). The response to sodium nitroprusside was also evaluated. In controls, vasodilation to bradykinin was inhibited by L-NMMA and remained unchanged by ouabain or vitamin C. In hypertensive patients, vasodilation to bradykinin was blunted and resistant to L-NMMA but sensitive to ouabain. Vitamin C increased the response to bradykinin and restored the inhibiting effect of L-NMMA while preventing the effect of ouabain. In hypertensive patients, infusions were repeated after 3-month treatment with lercanidipine (10 to 20 mg daily). Lercanidipine decreased plasma lipoperoxides, isoprostanes, and malondialdehyde and increased plasma antioxidant capacity. Moreover, lercanidipine increased the vasodilation to bradykinin and restored the inhibiting effect of L-NMMA on bradykinin-induced vasodilation while preventing the effect of ouabain. Finally, vitamin C no longer exerted its facilitating activity. These results indicate that in essential hypertension, lercanidipine increases endothelium-dependent vasodilation by restoring NO availability and preventing hyperpolarization, an effect probably determined by antioxidant activity.
Hypertension 2003 Apr
PMID:Calcium antagonist treatment by lercanidipine prevents hyperpolarization in essential hypertension. 1295 20

The importance of measuring microalbuminuria is well established. However, only scanty data are available concerning the biological variability of albumin excretion in type 2 diabetic subjects. We report our experience from a large clinical trial of a new antihypertensive drug (Lercanidipine) designed to reduce albumin excretion and blood pressure in type 2 diabetic patients with hypertension and microalbuminuria. Eighty seven patients with persistent microalbuminuria were studied within 1 year of the clinical trial. The measurements were performed on blood and timed urine samples frozen at -80 degrees C and shipped to a central laboratory unit. Preliminary experiments were performed to assess albumin stability in urine under various conditions (4 degrees C, -20 degrees C and -80 degrees C), particularly with regard to the albumin/creatinine ratio. Urine samples can be stored up to 3 weeks at 4 degrees C or up to 2 months at -80 degrees C. The biological variability of the albumin excretion rate was 25.7%, while that of the albumin/creatinine ratio was 13.4%. These data are useful in defining the analytical goals of imprecision for microalbuminuria (CV = 13% for albumin, and CV = 6% for albumin/creatinine ratio). No correlation between albumin/creatinine ratio and HbA1c was found in the cohort of 61 microalbuminuric patients who completed the trial. The results of this study confirm that the albumin/ creatinine ratio is much more suitable for monitoring albumin excretion in longitudinal studies than the albumin excretion rate.
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PMID:Biological variability of albumin excretion rate and albumin-to-creatinine ratio in hypertensive type 2 diabetic patients. 1459 74


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