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Biomedical subjects

D Susic

Publications and source records attributed to D Susic.

At least 37 records · Page 2Linked to original sources
PubMed1995

Early genes induction in spontaneously hypertensive rats left ventricle with angiotensin-converting enzyme inhibitors but not hydralazine.

Spontaneously hypertensive rats were given an angiotensin-converting enzyme (ACE) inhibitor (benazepril or quinapril) or hydralazine and were left for up to 6 hr. To examine whether administration of antihypertensive agents affects expression of immediate early genes in left ventricular myocardium, groups of rats were sacrificed at 1, 3, and 6 hr after dosing; total RNA was extracted from left ventricular tissue and analyzed by blot hybridization technique using labeled probes for c-myc, c-fos, and GAPDH mRNA. All three antihypertensive agents reduced pressure similarly, and treatment with the two ACE inhibitors increased c-fos and c-myc mRNA expression in left ventriculum. By contrast, hydralazine did not increase steady-state mRNA expression of either proto-oncogene. Thus, in parallel with the pressure fall, acute administration of the ACE inhibitors induced expression of c-fos and c-myc mRNAs in the left ventricle. Since the equidepressor dose of hydralazine did not affect expression of these proto-oncogenes, this effect of ACE inhibitors is independent of their hemodynamic action.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Effects of captopril and hydralazine on progression of adriamycin nephropathy in spontaneously hypertensive rats.

The effects of captopril and hydralazine on morphologic changes and clinical course of adriamycin nephropathy in spontaneously hypertensive rats (SHR) were examined. The rats were followed for 18 weeks after adriamycin injections. At week 1 they were randomly assigned to receive no antihypertensive treatment, captopril 60 mg/kg per day or hydralazine 6 mg/kg per day. A control group of SHR not treated with adriamycin was also included in the study. Both antihypertensive agents normalized systemic blood pressure, but failed to prevent proteinuria, mesangial expansion and renal failure progression. At the end of the study all adriamycin-treated groups had the same degree of renal failure irrespective of whether blood pressure was well controlled with captopril or hydralazine or whether hypertension persisted. Nevertheless, antihypertensive therapy slowed down renal function deterioration in the early stage of adriamycin nephropathy. Treatment with captopril also reduced the development of glomerular sclerosis.

Animals↗
PubMed1993

Antihypertensive action of heparin: role of the renin-angiotensin aldosterone system and prostaglandins.

Chronic subcutaneous administration of heparin consistently lowers blood pressure in hypertensive rats. This antihypertensive effect is related at least in part to a concomitant decrease in hematocrit. Groups of spontaneously hypertensive (SHR) and normotensive Wistar (NWR) rats were treated with subcutaneous heparin (700 U/d) for 6 weeks. Weekly determinations of systolic blood pressure (tail-cuff) and hematocrit were done. Peripheral plasma renin activity, plasma aldosterone, plasma prostaglandins (PGs) (PGF2 alpha, PGI2), thromboxane A2, and urinary kallikrein were measured. Blood pressure responses of acute and chronic heparin treatment to vasoconstrictor substances, including angiotensin I, angiotensin II, and norepinephrine, were determined. As before, heparin produced a significant (P < .01) decrease in hematocrit in both SHRs and NWRs, but a parallel decrease in blood pressure was noted only in SHRs. A significant (P < .001) increase in plasma renin activity was found in heparin-treated SHRs and NWRs; however, a corresponding elevation of plasma aldosterone level was noted only in heparin-treated NWR. Plasma aldosterone level significantly (P < .01) decreased in heparin-treated SHRs. Plasma PGs and urinary kallikrein levels were not different among the groups. The blood pressure responses to vasoconstrictor substances were essentially similar among the heparin-treated and control groups. These findings suggest that PGs or kallikrein have a slight or no role in determining the antihypertensive effect of heparin. Conversely, the results suggest that a reduced aldosterone level contributes to the antihypertensive mechanism of heparin.

Aldosterone↗
PubMed1992

The effect of acute and chronic hematocrit changes on cardiovascular hemodynamics in spontaneously hypertensive rats.

Heparin given over a long term by a subcutaneous route consistently lowers blood pressure in the hypertensive rat models. The decrease in blood pressure is accompanied by a parallel decrease in hematocrit suggesting a causal relationship between hematocrit and blood pressure. The aim of this study was to define the relationships between acute and chronic hematocrit changes and blood pressure in the normotensive and hypertensive states. Normotensive Wistar (NWR) and spontaneously hypertensive (SHR) rats were used. Hematocrit was decreased acutely by blood-letting, and chronically by treatment with either heparin (H) or phenylhydrazine (P) for 4 weeks. Acute and chronic hematocrit increase was accomplished by packed cells transfusion. Systolic blood pressure was measured weekly; and at the end of the experimental period, plasma volume, cardiac output, and mean arterial pressure were obtained. Acute hematocrit decrease or increase (hematocrit ranging from 25 to 65%) did not affect blood pressure in either strain of rats; whereas chronic hematocrit changes (hematocrit ranging from 35 to 61%) significantly affected blood pressure only in SHR. Thus, chronic hematocrit decrease induced by H or P resulted in a significant fall in blood pressure compared to control (201 +/- 3 v 175 +/- 4, 167 +/- 4 mm Hg, respectively; P < .05). Conversely, a chronic hematocrit increase resulted in a significant rise in blood pressure (201 +/- 3 v 219 +/- 4 mm Hg; P < .05). Similar hematocrit changes produced in NWR, as in SHR, did not affect blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Streptozotocin-induced diabetes mellitus lowers blood pressure in spontaneously hypertensive rat.

There are conflicting reports showing that alloxan or streptozotocin-induced diabetes in rat increases, decreases or does not alter blood pressure. Since hypertension influences organ-specific diabetic complications, this study was designed to examine the effects of streptozotocin-induced diabetes on blood pressure (BP), hemodynamics and heart weight in spontaneously hypertensive (SHR) and normotensive Wistar (NWR) rats. In order to control the influence of weight loss on BP affected by diabetes, we have examined the effect of weight loss without diabetes on BP, hemodynamics and heart weight in SHR. Weight loss parallel to that in diabetic SHR was induced in a group of SHR by food restriction (fasting). Significant (P less than .05) decreases in systolic and direct BP were observed in diabetic SHR. This hypotensive effect was accompanied by a significant (P less than .05) decrease in total peripheral resistance, but no change in cardiac output. These blood pressure and hemodynamic findings in diabetic SHR were complimented by a significant (P less than .05) reduction in left ventricular weight to body weight ratio. On the contrary, fasting SHR with weight loss equivalent to that in diabetic SHR showed no change in BP or total peripheral resistance. Further, fasting SHR revealed a significant (P less than .05) increase in heart weight to body weight ratio. The weight loss of equal magnitude induced by streptozotocin-induced diabetes in NWR did not have any effect on BP or hemodynamics. In addition, like fasting SHR, diabetic NWR showed a significant (P less than .05) increase in left ventricular weight to body weight ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Prostaglandin synthesis inhibitors potentiate the antihypertensive effect of heparin in spontaneously hypertensive rats.

We have shown that heparin lowers blood pressure significantly in hypertensive rats. This study was initiated to examine whether prostaglandin (PG) mediates the antihypertensive action of heparin. To this end, the effect of three different PG synthesis inhibitors (indomethacin, aspirin, meclofenamate) on the cardiovascular and renal actions of heparin was studied in spontaneously hypertensive rats (SHR). During 4 weeks of treatment, heparin reduced blood pressure significantly (P less than 0.01) in SHR. This was accompanied by significant decrements in hematocrit and total peripheral resistance but a significant increment in cardiac output. All of the PG inhibitors used significantly potentiated the antihypertensive effect of heparin and further reduced blood pressure by about 20%. Although heparin alone increased plasma renin activity, heparin and PG inhibitors together prevented this effect. When compared with heparin-treated rats, SHR treated with heparin and PG inhibitors combined had significantly (p less than 0.05 to 0.01) lower plasma aldosterone levels. These levels, however, were not different from SHR treated with PG inhibitors alone. Like blood pressures, the renal histopathologic lesions in SHR treated with heparin or heparin and PG inhibitors combined were significantly less severe than those in untreated SHR or SHR treated with PG inhibitors alone. Finally, captopril was shown to potentiate the effect of heparin. In conclusion, the antihypertensive effect of heparin does not appear to be PG mediated, but may be related to the structural changes in renal arterioles, inhibition of angiotensin-converting enzyme, or both.

Aldosterone↗
PubMed1984

Morphometric studies on the rat renal papilla of resistant and sensitive strains in partial nephrectomy salt hypertension.

The renomedullary interstitial cell (RIC) was studied morphometrically in the partial nephrectomy-salt (Chanutin-Ferris) model of hypertension. The RIC were compared in four strains of rat, two of them being resistant to the induction of this form of hypertension and two of them being sensitive. The Dahl salt-resistant (R/JR) rat was compared to a commercial Sprague-Dawley (SD) strain, and a Wistar derived strain discovered in Belgrade by Susic and Kentera (WB) was compared to a commercial Wistar strain (W). In both studies, resistance and sensitivity correlated well with the state of the RIC before the experimental procedure, the resistant strain having more numerous and better granulated RIC than the sensitive strain. It may therefore be possible to predict salt-resistance or sensitivity in rats by morphological examination of the RIC.

Animals↗
PubMed1976

Salt-induced hypertension in rats with hereditary hydronephrosis: the effect of renomedullary transplantation.

The antihypertensive action of renomedullary autotransplantation was investigated in rats with unilateral hereditary hydronephrosis showing extensive destruction of the medulla of the affected kidney. All rats were divided into three groups and unilaterally nephrectomized. The first group consisted of rats with a normal kidney remaining. The second and third groups had the hydronephrotic kidney remaining and received renomedullary and renocortical autotransplants, respectively. After completion of baseline studies, all rats were given 1 per cent saline solution instead of drinking water, and relevant parameters were re-examined 14 days later. Significant increase in blood pressure (greater than 150 mm. Hg), extracellular fluid volume, and plasma volume were found in group 3 while no changes were detected in groups 1 and 2. After administration of aspirin (and presumed blockade of prostaglandin synthesis) significant increases in plasma and extracellular fluid volumes were detected in groups 1 and 2, but no change in blood pressure was found. The results show that renomedullary transplantation protects against salt-induced hypertension and further indicate that the renomedullary prostaglandins are not a likely mediator of the antihypertensive action of the renal medulla.

Animals↗
PubMed1975

The renin-angiotensin system in rats with hereditary hydronephrosis.

The renin-angotensin system was studied in rats suffering from hereditary hydronephrosis in which normal blood pressure, hyperkalemia, and damage to the renal medulla and distal tubules were found. An increased serum creatinine level, decreased creatinine clearance and increased 24 hrs urine volume were observed in rats with bilateral hydronephrosis. When compared to rats with normal kidneys, bilaterally hydronephrotic animals exhibited elevated plasma renin activity (9.9 +/- 1.3/S.E./ng AI/ml/hr vs. 2.4 +/- 0.4 in rats with normal kidneys), and decreased renal renin concentration (78 +/- 4 mug AII/g vs. 132 +/- 5). No correlation between the extent of kidney damage and renal renic concentration was found. After the hyperkalemia of the hydronephrotic rats was corrected, there were significant increases in both plasma renin activity and renal renin concentration, but the renal renin concentration remained significantly lower than that observed in animals with normal kidneys. The results suggest that renin production and/or storage capacity are diminished in hydronephrotic kidneys.

Angiotensin II↗
PubMed1975

Effects of aspirin on renal sodium excretion, blood pressure, and plasma and extracellular fluid volume in salt-loaded rats.

The effect of aspirin administration and presumed blockade of prostaglandin synthesis on renal sodium excretion, plasma and extracellular fluid volumes, and blood pressure were examined in rats on a high sodium intake. After acute salt loading aspirin treated rats showed an impaired sodium excretion, while no changes in glomerular filtration rate were observed. In chronically loaded rats (7 weeks) administration of aspirin induced significant increases in both plasma and extracellular fluid volume, but no significant changes in blood pressures were found. The results are consistent with the hypothesis that prostaglandins mediate renal sodium excretion and therefore participate in extracellular fluid volume regulation.

Animals↗
PubMed1975

Differentiation of nephrotensin from the renin angiotensin system.

An investigation of the relationship between nephrotensin and the renin angiotensin system was carred out. Nephrotensin was found in the plasma of rats with renal clip hypertension and with chemically induced kidney damage. There was no demonstrable correlation between presence of nephrotensin and plasma renin activity, and the pressor activity of nephrotensin was not altered by previous immunization of test animals with angiotensin II nor by pretreatment with angiotensin I converting enzyme inhibitor. These results indicate that nephrotensin is different from the components of the renin-angiotensin system.

Angiotensin II↗
PubMed1975

Rapid onset of salt induced hypertension in rats with hereditary hydronephrosis.

Rats with hereditary hydronephrosis and littermates with normal kidneys were given 1% saline solution instead of drinking water, and renal excretory function, blood pressure, fluid volumes, and plasma renin activity were monitored. A marked increase in blood pressure and positive correlation between blood pressure and plasma volume were found in hydronephrotic rats after five weeks of salt loading, while animals with normal kidneys remained normotensive. No involvement of the renin-angiotensin system could be demonstrated in the observed phenomenon. It is suggested that the impairment of renal excretory function along with the deficiency of antihypertensive reno-medullary factors are responsible for the greater sensitivity of the hydronephrotic rats to the hypertensive stimulus of salt overload.

Animals↗