Biomedical subjects

D Susic

Publications and source records attributed to D Susic.

At least 19 recordsLinked to original sources

PubMed2001

Isolated systolic hypertension in elderly WKY is reversed with L-arginine and ACE inhibition.

This study was designed to examine the preventability of progressive deterioration of cardiovascular structure and function in very old Wistar-Kyoto (WKY) rats with isolated systolic hypertension (ISH). To this end, male 18-month-old normotensive WKY rats were given either placebo or L-arginine (70 mg. kg(-1). d(-1)) and an ACE inhibitor (enalapril, 30 mg. kg(-1). d(-1)) for 6 months. These control and treated rats were studied at the age of 2 years by examining: cardiovascular mass and collagen content, cardiac function, and systemic and regional (including coronary) hemodynamics. Additional data obtained in adult, 35-week-old WKY are included for comparison. ISH associated with increased total peripheral resistance was found in the old, untreated WKY, and this was prevented by the combined treatment. The untreated rats also exhibited impaired left ventricular function, as denoted by increased left ventricular end-diastolic pressure and reduced maximal rates of rise and fall of left ventricular pressure. These functional changes were also ameliorated with the combined treatment. Coronary hemodynamics were also compromised in the untreated WKY; and therapy improved coronary flow reserve and minimal coronary vascular resistance in both ventricles of the old WKY in parallel with reduction of arterial pressure. Blood flow to various other organs was uncompromised in the old rats, although increased vascular resistances were observed in untreated old WKY with ISH. These changes were also improved by the combined therapy. Finally, therapy diminished left ventricular mass and collagen concentration in old WKY compared with the untreated WKY. However, when compared with the 35-week-old WKY, both groups of old WKY (untreated and treated) demonstrated myocardial fibrosis, depressed ventricular function, and compromised coronary hemodynamics. Therefore, L-arginine and ACE inhibitory therapy ameliorated the hypertensive and associated adverse cardiovascular changes in old WKY, although it failed to improve totally the progressive deterioration of cardiovascular structure and function that occurred with aging. The results suggest that different mechanisms may be responsible for the hypertension- and age-related cardiovascular changes, although they may appear to be similar.

Aging↗

PubMed2001

Heart, aging, and hypertension.

Hypertension and aging adversely affect cardiovascular system and the heart is invariably involved. Manifestations of hypertensive heart disease and of the aging heart appear similar; ventricular hypertrophy, myocardial fibrosis, and impairments in ventricular function and coronary hemodynamics characterize both conditions. However, a great deal of evidence suggests that different underlying pathophysiological mechanisms may be involved. This report discusses most recent clinical and experimental findings and focuses on the alterations in nonmyocytic elements that are a part of heart involvement. Particular attention was given to factors that are responsible for exaggerated myocardial deposition of collagen that, by itself, may be responsible for ventricular dysfunction and impaired coronary hemodynamics in hypertensive and aging hearts. Newly developed therapeutical strategies, based on the most recent experimental and clinical studies, are also discussed.

Aging↗

PubMed2001

Abnormal renal vascular responses to dipyridamole-induced vasodilation in spontaneously hypertensive rats.

The objective of this study was to determine whether there were differences in hemodynamic responses of different vascular beds to systemic administration of dipyridamole between spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. To this end, systemic hemodynamics and organ blood flows (using labeled microspheres) were determined in conscious rats before and 10 minutes after dipyridamole (4 mg. kg(-1). min(-1)) infusion. In both the normotensive and hypertensive rats, the dipyridamole infusion reduced arterial pressure by approximately 20 mm Hg, associated with a decreased total peripheral resistance and an increased cardiac output. Renal blood flow decreased significantly in SHR after dipyridamole but remained unchanged or increased slightly in the WKY rats. There were no other differences in regional hemodynamics, including those of brain, liver, skin, and muscle, between the WKY and SHR. Antihypertensive treatment completely restored normal renal vascular response to dipyridamole. Previous reports had demonstrated an abnormal coronary hemodynamic response of the SHR. Our data demonstrate that, as with coronary hemodynamics, hypertension selectively induced alterations in renal vasculature. These findings may be of importance in identifying the earliest hemodynamic evidence of developing hypertensive nephrosclerosis.

Animals↗

PubMed2001

Coronary hemodynamic and ventricular responses to angiotensin type 1 receptor inhibition in SHR: interaction with angiotensin type 2 receptors.

This study was designed to determine the effects of angiotensin II type 1 (AT(1)) receptor inhibition on coronary hemodynamics and ventricular mass and hydroxyproline content and the additive effects of angiotensin II type 2 (AT(2)) receptor inhibition in spontaneously hypertensive rats (SHR). The selective AT(1) receptor antagonist candesartan (10 mg/kg per day) was administered alone or in combination with the AT(2) receptor antagonist PD 123319 (50 mg/kg per day) for 12 weeks. Control SHR received placebo for the same period. Left and right ventricular coronary blood flow, blood flow reserve, and minimal coronary vascular resistance were determined by using radiomicrospheres in male 35-week-old rats. Mean arterial pressure; total peripheral resistance; left and right ventricular, renal, and aortic weights; and hydroxyproline concentration were also determined. Candesartan reduced mean arterial pressure and left ventricular, renal, and aortic masses, as well as hydroxyproline concentration and minimal coronary vascular resistance of both ventricles. PD 123319 partially prevented the hypotensive effect of AT(1) receptor inhibition and reversed the effect on myocardial hydroxyproline concentration. These data suggest that AT(2) receptors contribute to the hypotensive and antifibrotic effects but not the coronary hemodynamic improvement or reduced left ventricular mass of AT(1) receptor inhibition in these adult SHR.

Angiotensin Receptor Antagonists↗

PubMed2001

Low-dose ACE with alpha- or beta-adrenergic receptor inhibitors have beneficial SHR cardiovascular effects.

BACKGROUND: There are no data regarding the prolonged effect of alpha-1 adrenergic receptor antagonists on ventricular collagen content and coronary hemodynamics in spontaneously hypertensive rats (SHR). This study, therefore, was designed to determine the effects of chronic treatment with the alpha-1 adrenergic receptor inhibitor doxazosin on SHR systemic and regional (especially coronary) hemodynamics, cardiovascular mass, and ventricular collagen. The effects of the combination of doxazosin with low-dose angiotensin-converting enzyme inhibitor were studied versus the alpha-1 antagonist alone. These effects were compared with those of a beta-1 adrenergic receptor inhibitor. METHODS AND RESULTS: Systemic and regional hemodynamics (radionuclide-labeled microspheres), left and right ventricular weight, hydroxyproline concentration, and aortic weight were measured at age 35 weeks. Doxazosin reduced arterial pressure and total peripheral resistance without changing left ventricular mass and collagen content, whereas monotherapies with the beta-1 antagonist metoprolol or a subdepressor dose of the ACE inhibitor enalapril were effective in reducing left ventricular mass and hydroxyproline without altering pressure. Doxazosin combined with the same low-dose ACE inhibitor reduced left ventricular mass and hydroxyproline without potentiating the hypotensive effect of doxazosin. By contrast, the combination of beta-1 antagonist with the low-dose ACE inhibitor reduced pressure, unlike either agent alone. Aortic weight index was significantly reduced only by doxazosin whether when used alone or with the ACE inhibitor. Low-dose ACE inhibitor with doxazosin or the beta-1 receptor antagonist as well as doxazosin alone decreased renal vascular resistance. CONCLUSION: These data show that the low subdepressor dose ACE inhibitor with an alpha- or beta-adrenergic receptor antagonist provides beneficial cardiovascular effects in SHR.

Adrenergic alpha-Antagonists↗

PubMed2000

Hypertension and the heart.

Sustained increase in arterial pressure causes left ventricular hypertrophy and adversely affects all myocardial compartments: myocytes, interstitium, and coronary vasculature. Ventricular hypertrophy significantly increases the risk for cardiovascular morbidity and mortality in hypertensive disease. Impairments in coronary circulation and ventricular fibrosis, which are an essential part of hypertensive disease, contribute to that increased risk. This report discusses the mechanisms of hypertension-induced myocardial collagen accumulation and impairments in coronary hemodynamics. Particular attention is given to the interaction of hypertension and aging because aging aggravates hypertensive changes and the incidence of hypertension increases with aging. The effect of therapy on hypertension-induced ventricular fibrosis and impairment in coronary hemodynamics and the risk associated with these changes are also discussed.

Aging↗

PubMed2000

Renal protective potential of antihypertensive drugs.

The objective of this review is to discuss recent experimental and clinical data concerning the effectiveness of antihypertensive drugs in preventing or delaying renal changes caused by diabetes mellitus and hypertension and to examine possible future developments. A brief description of the mechanisms involved in the development of renal failure in diabetes and hypertension is included. Evidence is presented to show that in addition to renoprotection offered by reduction in arterial pressure, some antihypertensive agents may give more nephroprotection. This added renoprotective potential of antihypertensive agents, which are either already in use or are being developed, is discussed. The nephroprotective action of conventional antihypertensive drugs, such as beta-blockers, calcium antagonists and angiotensin-converting enzyme inhibitors is briefly reviewed. It is noted that several studies indicate that angiotensin-converting enzyme inhibitors may be more effective in preventing or retarding renal failure than other conventional drugs. The renoprotective potential of newly developed agents, such as angiotensin II Type 1 receptor antagonists, vasopeptidase inhibitors and endothelin receptor antagonists is also examined. Emphasis is placed on a possible superior renoprotective effect of combination therapy over monotherapy.

Adrenergic beta-Antagonists↗

PubMed1999

Ultrasonography may be misleading in the diagnosis of ruptured and dislocated ulnar collateral ligaments of the thumb.

To find out if a non-invasive technique (ultrasonography) was able to identify a dislocated ligament of a metacarpophalangeal joint of the thumb with instability of the ulnar collateral ligament, 14 consecutive patients with clinical rupture of the ulnar collateral ligament were examined with ultrasonography before the ligament was explored. At exploration all ligaments were ruptured, and only five out of the 14 were dislocated. Ultrasonography recognised only two of the dislocated ligaments, and in half of the 14 patients the ultrasound scan gave incorrect information about the position of the ligament. We conclude that ultrasonography is not adequate for identifying dislocated ulnar collateral ligaments of the metacarpophalangeal joint of the thumb, and exploration is indicated in those with clinical instability in which palpation either suggests a dislocated ligament or is inconclusive.

Collateral Ligaments↗

PubMed1999

Pharmacologic agents on cardiovascular mass, coronary dynamics and collagen in aged spontaneously hypertensive rats.

OBJECTIVE: To determine whether antihypertensive treatment could alter hypertension and age-related progressive impairment of coronary hemodynamics and cardiac fibrosis in aged spontaneously hypertensive rats (SHR). DESIGN: Old SHR were given their respective therapy for 3 months. To differentiate between hypertension and age-related changes, a comparison was made between left and right ventricular indices since the right ventricle was not exposed to pressure overload. METHODS: Male, 65-week-old spontaneously SHR were divided into three groups and were given either vehicle, felodipine (30 mg/kg per day) or enalapril (30 mg/kg per day). After 12 weeks of the respective treatments, systemic and coronary hemodynamics (radionuclide-labelled microspheres), right and left ventricular and aortic mass indices, and right and left ventricular hydroxyproline concentrations (an estimate of collagen) were determined. RESULTS: Arterial pressure and total peripheral resistance were reduced to the same extent in SHRs treated with either felodipine or enalapril; however, compared to the control rats, enalapril was more effective in reducing left ventricular and aortic mass indices. Both agents also improved coronary hemodynamics of both ventricles in aged SHR but enalapril was more effective as indicated by a greater increase in coronary flow reserve and a greater decrease in minimal coronary vascular resistance. Furthermore, enalapril but not felodipine reduced left ventricular hydroxyproline concentration; and right ventricular hydroxyproline concentration increased with felodipine but remained unchanged with enalapril. CONCLUSIONS: Both enalapril and felodipine ameliorated adverse cardiovascular effects of hypertension in the aged SHRs within 12 weeks, as demonstrated by reduced arterial pressure, diminished left ventricular mass, and improved coronary hemodynamics. Enalapril also decreased aortic mass and left ventricular collagen concentration and appeared to be more effective in improving coronary hemodynamics than felodipine, possibly as a result, in part, of reduced myocardial fibrosis.

Aging↗

PubMed1999

Prolonged L-arginine on cardiovascular mass and myocardial hemodynamics and collagen in aged spontaneously hypertensive rats and normal rats.

This study was designed to examine whether L-arginine could prevent hypertension- and age-related impairment of coronary hemodynamics and cardiac fibrosis in aged (80-week-old) rats. To differentiate between hypertension- and age-related changes, the study was performed in both normotensive Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHR). Male 1-year-old rats of both strains were divided into 2 groups and given either placebo or L-arginine (1.2 g/L) in drinking water. After 6 months, systemic and coronary hemodynamics (radionuclide-labeled microspheres), right and left ventricular and aortic mass indexes, and ventricular hydroxyproline (an estimate of collagen) concentrations were determined. In the aged WKYs, L-arginine did not affect any of the examined variables except slightly reducing total peripheral resistance. In contrast, L-arginine diminished arterial pressure, total peripheral resistance, and left ventricular and aortic mass indexes in the SHRs; it also increased coronary flow reserve and reduced minimal coronary flow resistance and myocardial hydroxyproline concentration. These findings demonstrated that L-arginine ameliorated adverse cardiovascular effects of hypertension in aged SHRs, as demonstrated by reduced arterial pressure and total peripheral resistance, diminished left ventricular mass and collagen content, and improved coronary hemodynamics. There were no important effects in the old WKYs.

Aging↗

PubMed1998

Coronary hemodynamics in aging spontaneously hypertensive and normotensive Wistar-Kyoto rats.

OBJECTIVE: To delineate hypertension-related and age-related changes in coronary hemodynamics and to assess the role of myocardial (i.e. left ventricular) hypertrophy and cardiac fibrosis in inducing progressive deterioration of coronary flow reserve associated both with hypertension and with aging. METHODS: Systemic and coronary hemodynamics (using radionuclide-labeled microspheres), right ventricular, left ventricular, and aortic mass indexes, and ventricular hydroxyproline concentrations (an estimate of collagen) in normotensive Wistar-Kyoto and spontaneously hypertensive rats aged 22, 35, and 65 weeks were determined. RESULTS: Spontaneously hypertensive rats of all ages had greater left ventricular and aortic masses, greater collagen concentrations in both ventricles, a lower coronary flow reserve, and greater minimal coronary vascular resistance after administration of dipyridamole than did Wistar-Kyoto rats. Despite spontaneously hypertensive rats having only left ventricular hypertrophy, coronary hemodynamics were impaired to the same extent in both ventricles. Progressive increases in myocardial collagen concentration, decreases in coronary flow reserve, and increases in minimal coronary vascular resistance were observed in rats of both strains with aging. A positive correlation and linear regression between myocardial collagen concentration and minimal vascular resistance were found for both ventricles of rats of both strains. CONCLUSIONS: Both aging and hypertension adversely affected the coronary circulation; furthermore, these effects appeared to be additive. Cardiac fibrosis, but not hypertrophy, might play a role in progressive deterioration of coronary hemodynamics in aging and hypertension and could provide an explanation for the diastolic dysfunction encountered clinically in older patients with hypertension.

Aging↗

PubMed1998

Nephroprotective effect of antihypertensive drugs in essential hypertension.

BACKGROUND: Effective antihypertensive treatment has prevented target-organ involvement in hypertension, markedly reducing morbidity and mortality from strokes, coronary heart disease, cardiac failure, and hypertensive emergencies. However, the incidence of hypertension-related end-stage renal disease continues to increase, suggesting that therapeutic reduction in arterial pressure by itself is not sufficient to prevent the development of hypertensive renal failure. OBJECTIVE: To examine experimental and clinical data concerning the protective effect of reduction of arterial pressure on the progression of hypertension-related renal disease, and the evidence indicating that some antihypertensive agents may afford more nephroprotection, over and above that attributable to reduction of arterial pressure. RESULTS: Results of numerous studies clearly indicate that adequate control of arterial pressure, irrespective of the antihypertensive agent used, slowed the progression of renal disease. Results of some studies suggest that lowering arterial pressure below the level that is usually considered adequate has an additional beneficial effect by slowing the progression of renal injury. CONCLUSION: Results of a number of studies evaluating nephroprotective effects of various drugs and regimens have indicated that certain agents, most notably angiotensin converting enzyme inhibitors and their combination with calcium antagonists, afford more protection than do others at similar levels of reduction of arterial pressure. Results of still other studies suggest that certain agents that exert greater nephroprotection are more efficient at controlling arterial pressure. Therefore, further data are needed before any final conclusion can be drawn. However, it is clear that, in order to establish nephroprotection in patients with essential hypertension, the problem should not be further complicated by additional comorbid diseases such as diabetes mellitus.

Animals↗

PubMed1997

Hypertension, aging, and atherosclerosis. The endothelial interface.

Hypertension, atherosclerosis, and aging are considered major independent risk factors for cardiovascular morbidity and mortality. Although independent as risk factors, the three entities are closely related and often operate simultaneously to affect the cardiovascular system adversely, resulting in damage to various organs. This article evaluates the evidence that endothelial damage may be the underlying pathophysiologic mechanism that connects the three entities.

Aging↗

PubMed1997

ACE inhibition reduces left ventricular mass independent of pressure without affecting coronary flow and flow reserve in spontaneously hypertensive rats.

Systemic and regional (including coronary) hemodynamics were studied in spontaneously hypertensive and normotensive Wistar Kyoto rats after 3 weeks of treatment with one of the three doses of the angiotensin converting enzyme inhibitor, ramipril. The effects of respective treatments on cardiovascular mass and systemic, coronary, and regional hemodynamics (at rest, during maximal treadmill exercise, and during dipyridamole infusion) then were evaluated in conscious rats using radiomicrosphere techniques. Low-dose ramipril (10 micrograms/kg/day by gavage) neither decreased arterial pressure nor reduced cardiac mass. However, medium (100 micrograms/kg/day) and high (1 mg/kg/day) doses reduced total cardiac and left ventricular masses to the same extent in spontaneously hypertensive rats, despite a much greater fall in arterial pressure with a high dose. Resting cardiac index, and myocardial and all other organ blood flows remained unchanged in both strains. When compared with Wistar Kyoto rats, coronary circulation was impaired in untreated spontaneously hypertensive rats (ie, reduced coronary flow and flow reserve and increased minimal coronary vascular resistance during dipyridamole infusion). This remained unchanged by ramipril. Furthermore, significant (and comparable) increases in cardiac index and myocardial blood flow and decreases in coronary vascular resistance were produced by maximal treadmill exercise in both strains. This also was unaffected by ramipril. These data showed that angiotensin converting enzyme inhibition with suboptimal and optimal hypotensive doses of ramipril reversed left ventricular hypertrophy in spontaneously hypertensive rats, but coronary flow, flow reserve, and minimal coronary vascular resistance remained unchanged despite left ventricular hypertrophy reversal.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

Enalapril and losartan reduced cardiac mass and improved coronary hemodynamics in SHR.

Among the multiple mechanisms postulated for the increased risk of hypertensive left ventricular hypertrophy (LVH), coronary hemodynamic alterations remain a strong possibility. This study was designed to compare the effects of treatment with an ACE inhibitor (enalapril) and an angiotensin AT1 receptor antagonist (losartan) on systemic and coronary hemodynamics and to determine whether the combination of these two renin-angiotensin system (RAS) inhibitor would be as or more effective in reducing mean arterial pressure (MAP), left ventricular (LV) mass, and improving coronary hemodynamics than either regimen alone. Thus, 23 week old spontaneously hypertensive rats (SHR) were treated (12 weeks) with tap water (C), enalapril (30 mg.kg-1.d-1), losartan (30 mg.kg-1.d-1), or their combination (15 mg.kg-1.d-1). Age-matched Wistar-Kyoto (WKY) rats served as normotensive controls. After 12 weeks, systemic and coronary hemodynamics were determined (15 microns radiolabeled microspheres) at baseline, during maximal treadmill exercise, and during maximal dilation (dipyridamole). Enalapril and losartan equally reduced MAP and LV mass in association with a decreased total peripheral resistance. The RAS combination reduced MAP and LV mass more than either drug alone. Resting cardiac index and coronary blood flow (CBF) per unit of LV mass did not differ among the groups. Although enalapril did not improve coronary flow reserve (CFR), it diminished minimal coronary vascular resistance (MCVR); losartan improved both. However, the combination was more effective than either agent alone, reaching values close to normotensive WKY controls. In conclusion, these data demonstrated significantly impaired maximal CBF, CFR, and MCVR in untreated SHR, but losartan alone and in combination with enalapril improved systemic and coronary hemodynamics more than enalapril alone.

Angiotensin Receptor Antagonists↗

PubMed1996

Losartan reduces cardiac mass and improves coronary flow reserve in the spontaneously hypertensive rat.

OBJECTIVES: To evaluate the effects of losartan administration on cardiovascular mass, systemic and coronary hemodynamics (rest, maximal treadmill exercise, and dipyridamole infusion) and on resting regional hemodynamics in conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. RESULTS: Although losartan administration (two doses: 10 and 30 mg/kg per day for 3 weeks by gavage) reduced left ventricular mass at the higher dose in WKY rats and with both doses in SHR, only the higher dose reduced arterial pressure in SHR. Losartan administration did not affect cardiac index, myocardial or other organ flows (radiomicrosphere) at rest in both strains. Significant increases in cardiac index and coronary flow and decreases in coronary vascular resistance were observed during exercise in both strains and these responses were not affected by losartan administration. Compared with those in WKY rats, coronary flow and flow reserve (dipyridamole) were decreased and minimal coronary vascular resistance was increased in untreated SHR. Administration of a higher losartan dose increased coronary flow reserve and decreased minimal coronary vascular resistance (measured during dipyridamole infusion) in SHR. CONCLUSIONS: These data demonstrated that losartan administration reduced left ventricular mass, a response that did not seem to be solely dependent on afterload. Furthermore, cardiac and stroke indices and coronary flow reserve were not changed in SHR during maximal treadmill exercise after hypertrophy reversal, even with the lower dose of losartan and when the ventricular afterload was similar to that of untreated SHR.

Angiotensin II↗

PubMed1996

Angiotensin II increases left ventricular mass without affecting myosin isoform mRNAs.

We studied the effect of chronic (7 days) angiotensin II (Ang II) infusion in nonpressor and pressor doses on cardiovascular mass and expression of alpha- and beta-myosin heavy chain genes in the left ventricle in normotensive Wistar rats. An increased left ventricular mass was observed in rats receiving non-pressor and pressor doses of Ang II, but only high doses increased arterial pressure. Normalization of arterial pressure during Ang II infusion by losartan, a specific Ang II receptor antagonist, or hydralazine had different effects on left ventricular mass. Losartan prevented the increased left ventricular mass, and hydralazine did not affect left ventricular mass. Northern blot analysis showed that the switch in left ventricular myosin isoform mRNA from the adult to the fetal pattern occurred only in rats given the pressor Ang II dose. Both losartan and hydralazine, in parallel with the normalization of arterial pressure, prevented this myosin isoform switch. Thus, these data suggest that the Ang II-induced increase in left ventricular mass was not dependent on pressure overload, but the switch in myosin isoform mRNA from the adult to the fetal pattern was dependent on pressure overload.

Angiotensin II↗

PubMed1995

Reversal of hypertrophy: an active biologic process.

Evidence from in vivo, in vitro, and genetic studies suggests that the reversal as well as the development of left ventricular hypertrophy do not depend solely on hemodynamic load; other factors are involved. Several humoral agents that may affect mitogenesis of cardiac myocytes and nonmyocitic elements have been identified, including the local renin-angiotensin system, norepinephrine, endothelins, transforming growth factor beta, insulin-like growth factor, bradykinin, prostaglandins, and nitric oxide. Animal studies using various models of left ventricular hypertrophy are beginning to suggest that reversal of hypertrophy may decrease mortality, improve coronary flow reserve, and maintain cardiac performance. Studies in humans are less supportive, and more are needed before it may be concluded that reduction of left ventricular mass decreases the cardiovascular morbidity and mortality associated with cardiac hypertrophy.

Animals↗