This paper is only available as a PDF. To read, Please Download here.
Abstract
Increased myocardial mass (cardiac hypertrophy, left ventricular hypertrophy [LVH])
is an example of the widespread structural cardiovascular changes, often referred
to as remodeling, that may be present in association with sustained high blood pressure.
LVH strongly predicts myocardial infarction, stroke, and cardiovascular death in patients
with hypertension. As a result, prevention or reversal of hypertensive LVH is widely
accepted as a desirable therapeutic goal. Although the molecular mechanisms responsible
for remodeling are unclear, it is believed that mechanical, endocrine, paracrine,
and autocrine factors control the remodeling process. Certain antihypertensive drugs
may have particularly favorable long-term effects in that they prevent and correct
these structural changes in addition to reducing arterial pressure. However, the mechanism
by which they achieve these effects is not well understood. It is theorized that angiotensin-converting
enzyme inhibitors do so by preventing the generation of growth-promoting/mitogenic
peptides and that beta-blockers interfere with the growth-promoting effects of catecholamines.
In experimental models, the selective blockade of T-type calcium-ion (Ca2+) channels with mibefradil has been demonstrated to have antiproliferative effects
in both the renal and cardiac vasculature; in patients with LVH, mibefradil reduced
the left ventricular mass index. Therefore, blockade of T-type Ca2+ channels may be useful in the prevention or regression of cardiovascular remodeling.
However, further research will be required before the clinical implications of these
findings can be assessed.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical TherapeuticsAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Patterns of left ventricular hypertrophy and geometric remodeling in essential hypertension.J Am Coll Cardiol. 1992; 19: 1550-1558
- Cardiac hypertrophy: Mechanical, neural, and endocrine dependence.Circulation. 1991; 83: 13-25
- Heart failure from the point of view of quantitative anatomy.Am J Cardiol. 1960; 5: 370-382
- Ventricular remodeling after myocardial infarction: Experimental observations and clinical implications.Circulation. 1990; 81: 1161-1172
- Clinical and morphological features of human hypertensive-diabetic cardiomyopathy.Am Heart J. 1980; 99: 446-458
- Myocardial disease in hypertensive-diabetic patients.Am J Med. 1989; 87 (Suppl 6A): 23S-28S
- A comparison of the pathological spectrum of hypertensive, diabetic, and hypertensive-diabetic heart disease.Circulation. 1990; 82: 848-855
- Interaction between alcohol and antioxidants.in: Alcohol and the Cardiovascular System. National Institutes of Health, Bethesda, Md1996: 441-457 (Research Monograph No. 31)
- Structure and function of small arteries.Physiol Rev. 1990; 70: 921-961
- Exacerbation of atherosclerosis by hypertension. Potential mechanisms and clinical implications.Arch Intern Med. 1996; 156: 1952-1956
- Effects of protection from pressure on resistance artery morphology and reactivity in spontaneously hypertensive and Wistar-Kyoto rats.Circ Res. 1991; 68: 1230-1240
- Importance of adaptive changes in vascular design for establishment of primary hypertension, studied in man and in spontaneously hypertensive rats.Circ Res. 1973; 32 (Suppl I): I2-I16
- Physiological aspects of primary hypertension.Physiol Rev. 1982; 62: 347-504
- Remodeling of cerebral arterioles in chronic hypertension.Hypertension. 1989; 13: 968-972
- Small artery structure in hypertension: Dual processes of remodeling and growth.Hypertension. 1993; 21: 391-397
- Regulation of smooth muscle cell growth by endothelium-derived factors.Tex Heart Inst J. 1994; 21: 91-97
- The pathogenesis of atherosclerosis—an update.NEJM. 1986; 314: 488-500
- Echocardiographically detected left ventricular hypertrophy: Prevalance and risk factors.Ann Intern Med. 1988; 108: 7-13
- Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension.Ann Intern Med. 1991; 114: 345-352
- Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study.NEJM. 1990; 322: 1561-1566
- Ventricular functions and coronary hemodynamics in hypertensive heart disease.Am J Cardiol. 1979; 44: 999-1006
- Hypertension and sudden death: Increased ventricular ectopic activity in left ventricular hypertrophy.Am J Med. 1984; 77: 18-22
- Rapid ventricular filling in left ventricular hypertrophy. II: Pathologic hypertrophy.J Am Coll Cardiol. 1985; 5: 862-868
- Assessment of left ventricular function by the midwall fractional shortening/end-systolic stress relation in human hypertension.J Am Coll Cardiol. 1994; 23: 1444-1451
- Impaired left ventricular functional reserve in hypertensive patients with left ventricular hypertrophy.Hypertension. 1989; 14: 1-8
- The progression from hypertension to congestive heart failure.JAMA. 1996; 275: 1557-1562
- Unrecognized myocardial infarction and hypertension: The Framingham study.Am Heart J. 1985; 109: 581-585
- Heterogeneity of the atherosclerotic process in systemic hypertension poorly controlled by drug treatment.Am J Cardiol. 1987; 59: 414-417
- The Lausanne Stroke Registry: Analysis of 1,000 consecutive patients with first stroke.Stroke. 1988; 19: 1083-1092
- Regression of cardiovascular structural changes—a preventive strategy.Clin Exp Hypertens. 1990; 12A: 877-896
- Reversal of left ventricular hypertrophy in hypertensive patients: A metaanalysis of 109 treatment studies.Am J Hypertens. 1992; 5: 95-110
- Reversal of left ventricular hypertrophy in essential hypertension: A meta-analysis of randomized double-blind studies.JAMA. 1996; 275: 1507-1513
- Cyclic AMP and the induction of eukaryotic gene transcription.J Biol Chem. 1988; 263: 9063-9066
- Norepinephrine induces the raf-1 kinase/mitogen-activated protein kinase cascade through both alpha-1 and beta-adrenoreceptors.Circulation. 1997; 95: 1260-1268
- Angiotensin-converting enzyme inhibition and ventricular remodeling after myocardial infarction.Annu Rev Physiol. 1995; 57: 805-826
- Ventricular remodeling and angiotensin-converting enzyme inhibitors.J Cardiovasc Pharmacol. 1994; 24 (Suppl 3): S27-S31
- Effects of ACE inhibitors on circulating versus cardiac angiotensin II in volume overload-induced cardiac hypertrophy in rats.Circulation. 1995; 92: 3568-3573
- Disparate effects of antihypertensive drugs on large artery distensibility and compliance in hypertension.Am J Cardiol. 1995; 76 (Suppl): 46E-49E
- Role of hypertension in coronary artery disease.Am J Nephrol. 1996; 16: 210-216
- Vascular remodeling in coronary artery disease.J Cardiovasc Pharmacol. 1994; 24 (Suppl 3): S5-S15
- Vascular wall thickness in hypertension: The Perindopril Regression of Vascular Thickening European Community Trial: PROTECT.Am J Cardiol. 1995; 76 (Suppl): 50E-54E
- Regression of media-to-lumen ratio of human subcutaneous arteries and left ventricular hypertrophy during treatment with an angiotensin-converting enzyme inhibitor-based regimen in hypertensive patients.Am J Cardiol. 1995; 76 (Suppl): 38E-40E
- Antiatherogenic properties of calcium antagonists.Am J Med. 1989; 86 (Suppl 4A): 27-32
- Time courses of regression of vascular structural changes and its relation to cytosolic free calcium in hypertensives after nilvadipine treatment.J Hum Hypertens. 1995; 9: 735-739
- Receptor sites for Ca2+ channel antagonists.Trends Pharmacol Sci. 1992; 13: 256-262
- Calcium channel drugs: Structure-function relations and selectivity of action.J Cardiovasc Pharmacol. 1991; 18 (Suppl 10): S1-S6
- Ion channels as targets for drugs.in: Sperelakis N Cell Physiology Source Book. Academic Press, San Diego1995: 404-412
- Pharmacology of calcium channels in cardiac muscle, vascular muscle, and neurons.Am J Hypertens. 1991; 4: 406S-411S
- Endothelin-1 enhances calcium entry through T-type calcium channels in cultured neonatal rat ventricular myocytes.Circ Res. 1992; 71: 1242-1253
- Low-threshold current is major calcium current in chick ventricular cells.Am J Physiol. 1989; 256: H1505-H1508
- T-type Ca2+ current is expressed in hypertrophied adult feline left ventricular myocytes.Circ Res. 1993; 73: 777-782
- T-type Ca2+ channels are abnormal in genetically determined cardiomyopathic hamster hearts.Circ Res. 1994; 75: 149-155
- Voltage-dependent calcium entry in confluent bovine capillary endothelial cells.FEBS Lett. 1992; 299: 239-242
- Differential expression of voltage-gated Ca2+ currents in cultivated aortic myocytes.Biochim Biophys Acta. 1992; 1160: 95-104
- T-type calcium channels in adrenal glomerulosa cells: GTP-dependent modulation by angiotensin II.Proc Natl Acad Sci USA. 1993; 90: 3260-3264
- Increased cardiac types I and II collagen mRNAs in aldosterone-salt hypertension.Hypertension. 1994; 24: 30-36
- The angiotensin AT2 receptor modulates T-type calcium current in non-differentiated NG108-15 cells.FEBS Lett. 1992; 309: 161-164
- Ca2+ influx via T-type channels modulates PDGF-induced replication of mouse fibroblasts.Am J Physiol. 1993; 265: C1239-C1246
- Antihypertensive properties of the novel calcium antagonist mibefradil (Ro 40-5967): A new generation of calcium antagonists?.Hypertension. 1996; 27: 426-432
- Effects of a new calcium antagonist, mibefradil (Ro 40-5967), on silent ischemia in patients with stable chronic angina pectoris: A multicenter placebo-controlled study.J Am Coll Cardiol. 1996; 27: 317-322
- Selective inhibition of T-type Ca2+ channels by Ro 40-5967.Circ Res. 1994; 75: 144-148
- Mibefradil prevents neointima formation after vascular injury in rats: Possible role of the blockade of the T-type voltage-operated calcium channel.Arterioscler Thromb Vasc Biol. 1995; 15: 1161-1165
- Characteristics of angiotensin II receptors and their role in cell and organ physiology.in: Laragh J Brenner B 2nd ed. Hypertension: Pathophysiology, Diagnosis, and Management. Raven Press, New York1995: 1695-1720
- Modulation of [3H] dihydropyridine binding by activation of protein kinase C in vascular smooth muscle.Eur J Pharmacol. 1991; 208: 223-230
- Effects of calcium blockade on end-organ damage in experimental hypertension.J Hypertens. 1997; 15 (Suppl): S19-S30
- Increased survival after long-term treatment with mibefradil, a selective T-channel calcium antagonist, in heart failure.J Am Coll Cardiol. 1997; 29: 416-421
- The design of the Mortality Assessment in Congestive Heart Failure trial (MACH-1, mibefradil).Clin Cardiol. 1997; 20: 320-326
Article info
Identification
Copyright
© 1997 Published by Elsevier Inc.
