Renal phospholipase C and diglyceride lipase activity in spontaneously hypertensive rats

Phospholipase C activity and diglyceride lipase activity were studied in the renal cortex and medulla of 10- and 40-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched normotensive Wistar-Kyoto rats (WKY). Enhanced phospholipase C activity was found in the cortical and medullary cytosol of kidney from SHRSP, and microsomal diglyceride lipase in SHRSP also increased. In SHRSP, phospholipase C and diglyceride lipase activities increased with age, but this increase was not evident in WKY. Phospholipase C had high substrate specificity for phosphatidylinositol in renal cytosol of both WKY and SHRSP. The increased activities were accompanied by prostaglandin E2 synthesis in renal medullary microsomes of 10-week-old SHRSP and were also present in the kidney of 40-week-old SHRSP. Total phospholipid and arachidonic acid contents in kidney were markedly high in the medulla of 10-week-old SHRSP, but these lipids were decreased in 40-week-old SHRSP. These results suggest that phospholipids and arachidonic acid in SHRSP may be genetically high and that the activated phospholipase C and diglyceride lipase hydrolyze phospholipids, providing arachidonic acid for prostaglandin synthesis, which results in a decrease of phospholipids and arachidonic acid in the kidney of 40-week-old SHRSP. These studies demonstrate that a phosphatidylinositol-specific phospholipase C-prostaglandin synthetic system may play an important role in the course of hypertension in SHRSP.     

Plasma fatty acids and lipid hydroperoxides increase after antibiotic therapy in cystic fibrosis.

The present authors investigated whether cystic fibrosis is linked to a defect in fatty acids and assessed the impact of the main patients' characteristics on the levels of several fatty acids, mostly during respiratory exacerbation and after antibiotic therapy. Fatty acid phospholipid and cholesteryl ester levels were measured in stable-state patients and controls. No differences were found concerning either the fractions of palmitic and oleic acids or the cholesteryl esters of alpha-linolenic and arachidonic acids. However, phospholipids of alpha-linolenic and arachidonic acids, as well as cholesteryl esters and phospholipids of stearic and linoleic acids, were lower in patients than in controls, but fractions of dihomo-gamma-linolenic, docosatetraenoic, docosapentaenoic, palmitoleic and eicosatrienoic acids were higher. Fatty acid levels, oxidative stress markers, nutrients, body mass index and forced expiratory volume in one second (FEV(1)) were measured in patients before and after antibiotic courses for bronchial exacerbation. After adjustments, palmitic, stearic, alpha-linolenic, linoleic, arachidonic, palmitoleic and oleic acids generally decreased during exacerbation but almost all increased after antibiotic courses. Nearly all fractions increased along with FEV(1) and a positive relationship linked fatty acids to lipid hydroperoxides. There was no general drop in fatty acids. Patients' fatty acid profiles depended on the pulmonary function and the inflammation state.     

Contrasting effects of low or high copper intake on rat tissue lipid essential fatty acid composition

The effects of low copper intake or copper supplementation on the metabolism of stearic acid have been studied previously, but their effects on essential fatty acids have not been reported. Male Sprague-Dawley rats were fed for 12 weeks on pelleted semi-synthetic diets containing less than 1 mg/kg copper (low copper), 6 mg/kg (copper control), or 250 mg/kg copper (copper supplemented). The fatty acid composition of the total phopholipids and triglycerides of plasma, liver, heart and adipose tissue was analyzed by gas liquid chromatography. In low copper rats compared to controls, palmitic and oleic acids were decreased but stearic acid and docosahexaenoic acid were increased in plasma, liver and heart phopholipids. Arachidonic acid was also increased in plasma and liver phospholipids in low copper rats. In liver triglycerides, linoleic and arachidonic acids were increased but palmitic and oleic acid were decreased in low copper rats. Copper supplementation had the opposite effect; palmitic and oleic acids were increased in phospholipids and triglycerides whereas essential fatty acids were generally decreased. Hence, copper not only has a direct effect on the desaturation of stearic acid but also has significant effects on the tissue lipid composition of essential fatty acids.     

Metabolic effects of dietary stearic acid in mice: changes in the fatty acid composition of triglycerides and phospholipids in various tissues.

The fatty acid patterns of triglycerides and phospholipids extracted from adipose tissue, liver, heart, kidney, spleen, and lung of 3 groups of C57BL/6 mice were determined after feeding diets rich in palmitic acid (16:0) (high palmitic: 16:0 = 45.1% of total fatty acids), stearic acid (18:0) (high stearic: 18:0 = 42.9% of total fatty acids) and oleic acid (18:1) (high oleic: 18:1 = 79.7% of total fatty acids) for 9 months. Triglyceride content of adipose, liver, heart, kidney, lung and spleen tissues was significantly enriched in palmitic acid in mice fed the high palmitic diet (range among all tissues: 19.9% +/- 0.2% to 29.0% +/- 1.9% of total fatty acids) and in oleic acid in mice fed the high oleic diet (range 56.0% +/- 1.9% to 71.6% +/- 1.2%). The stearic acid content of organ triglycerides in mice fed the high stearic diet ranged from 3.7% +/- 0.3% to 10.8% +/- 1.2%; however, the content of oleic acid on this diet (range: 57.0% +/- 1.8% to 71.4% +/- 1.7%) was similar to the one observed in mice fed the high oleic diet. In all organs, phospholipids had a significantly higher percentage of stearic acid (range: 23.5% +/- 0.9% to 51.5% +/- 6.6%) than triglycerides, regardless of diet. To evaluate the production of oleate from stearate and palmitate, 2 groups of mice were fed the high palmitic and the high stearic diets for 1 week and then injected intravenously with [1-14C]palmitate and [1-14C]stearate and the amount of labelled oleate in liver triglycerides was measured.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased renal fatty acid binding protein in spontaneously hypertensive rats

The level of renal fatty acid binding protein (FABP) was quantified by a specific radial immunodiffusion method using an antibody to cytosolic FABP in stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) at 5, 10, 20 and 40 weeks of age. Increased levels were found in the SHRSP medulla, but not in the WKY medulla. The increase occurred in the hypertension development period, reaching a peak at 20 weeks of age. This increase was confirmed by immunoblotting. There was no significant change of FABP in the cortex. To elucidate the mechanism responsible for these changes in the FABP level, three antihypertensive drugs (nicardipine, hydralazine and enalapril) were given to SHRSP at 20 weeks of age for a period of four weeks. Antihypertensive treatment significantly inhibited the development of hypertension and the increase in the medullary FABP level. The differential response of FABP in SHRSP and WKY suggests that this protein may play an important role in the cellular metabolism of fatty acids under the pathological condition of high blood pressure.     

Biomechanical properties and chemical composition of the aorta in genetic hypertensive rats.

OBJECTIVE: To study the alteration in the biomechanical properties of the thoracic aorta and its composition in young normotensive Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHRSP). METHODS: The in-vitro biomechanical properties of the aorta in 4- and 12-week-old SHRSP were determined by means of a tensile testing machine and compared with those of the SHR and WKY rats; in addition, a biochemical analysis of collagen, elastin and advanced glycation endproducts was performed. RESULTS: The aortic biomechanical properties were altered in the 4- and 12-week-old SHRSP, compared with age-matched WKY rats and SHR. The maximum stress in the 12-week-old SHRSP was reduced by 27% compared with the normotensive WKY rats, and by 26% compared with the SHR. The maximum strain values in the 4- and 12-week-old SHRSP were lower than those in the age-matched WKY rats, by 12 and 9% respectively, whereas this value in the 12-week-old SHR was significantly increased (by 26%) compared with the age-matched WKY rats. No differences were observed in the aortic contents of collagen and elastin between the SHRSP and SHR. However, the extractability of collagen by pepsin digestion in the 12-week-old SHRSP was lower than that in the age-matched SHR and WKY rats, and a significantly larger accumulation of advanced glycation endproducts was observed in the 12-week-old SHRSP than in the age-matched SHR and WKY rats, suggesting a greater formation of collagen-derived cross-links in SHRSP. CONCLUSIONS: From these results, we conclude that decreased aortic distensibility and mechanical strength values are partly related to the greater formation of collagen-derived cross-links in 12-week-old SHRSP, and that the mechanical properties in SHRSP may be the result not only of the larger formation of collagen-derived cross-links but also of primary defects, since the aortic mechanical strength value was decreased even in 4-week-old SHRSP.     

Sustained contraction to angiotensin II and impaired Ca2+-sequestration in the smooth muscle of stroke-prone spontaneously hypertensive rats.

Contractile response to angiotensin II (AngII) of vascular smooth muscle was compared between 12-week-old, stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY). AngII induced phasic and tonic contraction in denuded aortic ring preparation. The phasic contraction was concentration-dependent (AngII 10(-9) to 10(-6) mol/L) and similar in both strains. However, the relaxation after phasic contraction was significantly attenuated in SHRSP compared with that in WKY. To examine the recovery of contractile responses to the repeated stimulation, AngII was applied three times at 20- and 60-min intervals. The first maximal contraction was similar in both strains, but the response to the second stimulation was significantly reduced in SHRSP, compared with all three responses in WKY. These results suggested that Ca2+-sequestration into the Ca2+ store is delayed in SHRSP. Cyclopiazonic acid (10(-5) mol/L), an intracellular Ca2+-pump inhibitor, decreased spontaneous relaxation and increased the sustained contraction in WKY, whereas it did not affect the contraction in SHRSP. Insulin, which modulates tonic contraction by facilitating Ca2+-extrusion, was applied at peak contraction by AngII. It enhanced relaxation after phasic contraction in a concentration-dependent manner in SHRSP, but it did not affect the relaxation in WKY. These results suggest that increased sustained contraction observed in SHRSP reflects at least partly the impaired Ca2+-pump activity leading to hypertension.     

Analysis of circadian blood pressure rhythm and target-organ damage in stroke-prone spontaneously hypertensive rats

OBJECTIVE: We compared diurnal patterns of blood pressure in Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP), and analyzed the relationship between the change in diurnal patterns of blood pressure and target-organ damage in SHRSP. MATERIALS AND METHODS: Blood pressure, heart rate and motor activity in the three groups of rats were continuously monitored by radiotelemetry, from 1100 h on the first measuring day to 1300 h on the third measuring day. The left ventricular weight and the ratio of beta-myosin heavy chain to alpha-myosin heavy chain in the cardiac left ventricle, morphological changes in the glomerular basement membrane in the kidney, 24 h urinary protein excretion and brain weights were also measured in 10-, 12- or 17-week-old SHRSP. RESULTS: The SHR circadian blood pressure rhythm exhibited a pattern which peaked during the rats' active (light-off or dark) phase, but the peak time was a little closer to the resting (light-on) phase compared with that for WKY rats. Although the circadian blood pressure rhythm for 10-week-old SHRSP was similar to that observed for SHR, the patterns in 12- and 17-week-old SHRSP were shifted further towards the resting phase. Heart and left ventricular weight increased with the progression of hypertension. The ratio of beta- to alpha-myosin heavy chain in the left ventricle was higher in 12- and 17-week-old SHRSP than in 10-week-old SHRSP. Brain weight was increased significantly in 17-week-old SHRSP compared with 10- and 12-week-old SHRSP. Increased urinary protein excretion and morphological changes in the glomerular basement membrane in the kidney were observed in 12- and 17-week-old SHRSP. CONCLUSIONS: These data suggest that SHRSP have an abnormal circadian blood pressure rhythm associated with hypertensive target-organ damage. This rat strain may therefore be a useful model in which to investigate the mechanisms responsible for the alteration in the circadian blood pressure rhythm, and to analyze the relationship between the abnormal circadian rhythm and target-organ damage.     

Effect of fatty acids on rat liver nuclear T3-receptor binding.

The effects of selected fatty acids (linoleic, oleic, and palmitic) on triiodothyronine (T3)-receptor binding were compared in isolated rat hepatocytes, rat liver nuclei, and receptor protein. Scatchard analysis indicated that the inhibition of T3-receptor binding by fatty acids was characterized by an increase in Kd and no change in maximum binding capacity (MBC). In isolated receptors, the rank order of potency for inhibition was linoleic acid greater than oleic acid greater than palmitic acid. The Ki for oleic acid in isolated receptors was the same as that for whole nuclei (15.4 +/- 1.3 v 16.3 +/- 1.9 mumol/L, respectively), indicating that the inhibition of nuclear T3 binding is probably at the level of the receptor protein itself. In isolated hepatocytes, linoleic acid was more potent than oleic acid in inhibiting T3 binding to nuclear receptors. Cell-associated T3 was not affected by the presence of fatty acids, implying that cellular uptake of T3 was not inhibited. High concentrations of fatty acids were necessary for inhibition of T3-receptor binding in isolated hepatocytes, with linoleic acid being one to two orders of magnitude less potent in isolated hepatocytes compared with isolated receptors (Ki, 179 +/- 12 v 4.4 +/- 0.5 mumol/L, respectively). It is concluded that the inhibitory effect of fatty acids on T3-receptor binding in isolated rat hepatocytes probably occurs at the level of the nuclear receptor, and does not involve an inhibition of the access of T3 to the receptor. However, in vivo it seems unlikely that fatty acids will have access to the nuclear receptors in sufficiently high concentrations to affect T3-receptor binding in liver cells.     

Endothelium-dependent responses of cerebral blood vessels during chronic hypertension

Acetylcholine produces less dilatation of pial arterioles in stroke-prone spontaneously hypertensive rats (SHRSP) than in normotensive (WKY) rats. Responses of cerebral vessels to acetylcholine and bradykinin appear to involve different mechanisms. Our first goal was to determine whether responses of pial arterioles to bradykinin are impaired in SHRSP. Diameter of pial arterioles (20-60 microns) was measured using intravital microscopy in WKY rats and SHRSP (9-12 months old). Superfusion of bradykinin (3 x 10(-7) M) dilated pial arterioles by 35 +/- 6% (mean +/- SEM) in WKY rats, but only 21 +/- 3% in SHRSP (p less than 0.05 versus WKY rats). Both nitric oxide (5 x 10(-7) M) and nitroglycerin (10(-5) M) produced similar vasodilatation in WKY rats and SHRSP. Our second goal was to determine whether alteration of postreceptor mechanisms contributes to impairment of endothelium-dependent cerebral vasodilatation in SHRSP. Calcium ionophore A23187 (10(-5) M) produced more vasodilatation in WKY rats than in SHRSP (32 +/- 8% versus 9 +/- 4%, p less than 0.05). Responses to A23187 (10(-5) M) were inhibited by indomethacin (46 +/- 13% versus 15 +/- 5%, p less than 0.05) in WKY rats, whereas responses to A23187 (10(-6) M) were potentiated modestly by indomethacin (-3 +/- 2% versus 4 +/- 2%, p less than 0.05) in SHRSP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Possible relationship between altered fatty acid composition of serum, platelets, and aorta and hypertension induced by sugar feeding in rats

To establish a relationship between alterations in fatty acid metabolism, induced by sugar ingestion, and hypertension, we analyzed fatty acid composition of serum, platelets and aorta in rats which had 30% of sugar in their drinking water for 18-20 weeks, and became hypertensive, hypertriglyceridemic and hyperinsulinemic. The fatty acid composition in sugar-fed as compared with that from control rats was as follows: in serum phospholipids, triglycerides and cholesterol ester fractions, palmitic, palmitoleic, oleic and cis-11-eicosadecaenoic acids were present in a higher proportion. In serum phospholipid fraction linoleic and arachidonic acids were decreased and a significant increase was observed in the proportion of dihomo-gamma-linolenic acid. In the membrane phospholipids of platelets and aorta, higher proportions of palmitoleic and of oleic acids were observed. Differences in fatty acid composition of phospholipids between sugar-fed and control rats are consistent with altered membrane fluidity. Altered membrane function is a potential mechanism involved hypertension in rats in sugar-induced.     

Genetic association of hypertension and vascular changes in stroke-prone spontaneously hypertensive rats

Isolated tail arteries from stroke-prone spontaneously hypertensive rats (SHRSP) exhibit oscillatory contractile activity in response to norepinephrine, whereas those from normotensive Wistar-Kyoto rats (WKY) do not. To determine whether the norepinephrine-induced oscillations are related to high blood pressure or to separable genetic differences between strains, the response to norepinephrine was studied in adult SHRSP, WKY, and progeny of genetic crosses of SHRSP and WKY (F1, F2, F1 X SHRSP, F1 X WKY). Helical tail artery strips were mounted in a tissue bath for isometric force recording. Rats were classified as responders if oscillatory activity in the presence of 1.8 X 10(-7) M norepinephrine exceeded 250 mg/10 min (milligrams of force amplitude during a 10-minute interval). The blood pressures (mm Hg +/- SEM; tail cuff method) and percentage of rats exhibiting norepinephrine-induced oscillations were as follows: WKY: 109 +/- 3, 0%; F1: 129 +/- 4, 0%; F2: 150 +/- 4, 38%; F1 X WKY: 137 +/- 3, 9%; F1 X SHRSP: 188 +/- 7, 71%; SHRSP: 207 +/- 7, 100%. The distribution of the frequency of animals with oscillatory activity among the progenies was consistent with the hypothesis that a single gene locus determines the observed difference in oscillatory activity between the WKY and SHRSP strains. The allele from the SHRSP that determines the activity phenotype is recessive to the allele contributed by the normotensive WKY strain. In the segregating F2 progeny, the blood pressure of the responders was higher than that of the nonresponders (161 +/- 6 vs 144 +/- 4 mm Hg; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

The fatty acid pattern of triglycerides and FFA in serum of spontaneously hypertensive rats (SHR).

The fatty acid patterns of serum triglycerides and FFA in SHR and in normotensive controls aged 4, 8 and 26 weeks were estimated by gas-liquid chromatography. In serum triglycerides of SHR, the percentage of linoleic acid (C18:2) was lower and the content of arachidonic acid (C20:4) higher than in age-matched control animals. A continuous increase in palmitic (C16) and linoleic acids as well as a decrease in arachidonic acid has been found with advancing age, the most striking differences existing between 4- and 8-week-old animals, i.e. before onset of arterial hypertension in SHR. In the pre-hypertensive stage, the percentage of arachidonic acid was about 3 times as high as in later stages in SHR. This gradation was, however, even more pronounced in normotensive control rats. The C18:2/C20:4-ratio of triglycerides was lower in SHR but increased with age in both groups reaching a 5--8-fold level. Similar behavior of the FFA fatty acid pattern was less marked. Alterations in levels of linoleic and arachidonic acids are of interest because of their pathogenic role as precursors of prostaglandins in the development of genetically spontaneous hypertension in rats. The results are discussed in connection with the hypotensive effect of a linoleic acid-rich diet recently reported in hypertensive rats.     

Inhibition of 3H-quinuclidinyl benzylate binding to cardiac muscarinic receptor by long chain fatty acids can be attenuated by ligand occupation of the receptor

Phospholipase A2 (PLA2) inhibits ligand binding to sarcolemmal muscarinic receptors in heart. To determine whether this effect of PLA2 is mediated by membrane accumulation of non-esterified fatty acids (FFA), the effect of selected fatty acids on the binding of 3H-quinuclidinyl benzylate (3H-QNB) to purified canine sarcolemmal membranes before and after PLA2 treatment was examined. Equilibrium 3H-QNB binding was inhibited by 5 min exposure of membrane vesicles to oleic, linoleic or arachidonic acid (IC50 = 6.3 +/- 0.9, 9.9 +/- 1.1, and 6.8 +/- 0.4 microM, respectively); the saturated fatty acids, stearic and palmitic acid (10 microM) had no effect. Scatchard analysis of equilibrium binding isotherms showed that the effect of the unsaturated fatty acids to inhibit 3H-QNB binding reflected a decrease of Bmax and a reduction of the affinity of the remaining receptors. The effect of unsaturated fatty acids was dependent on the mole ratio of fatty acid to membrane phospholipid present (FFA/PL ratio). Washing of fatty acid-treated membranes with bovine serum albumin (BSA) resulted in partial recovery of both maximal binding (Bmax) and affinity. The fatty acid-induced reduction of Bmax was also attenuated if binding was started by simultaneous addition of 3H-QNB and FFA. Similarity of the FFA induced effects on 3H-QNB binding to sarcolemmal muscarinic receptors to those induced by PLA2 suggest that membrane accumulation of unsaturated fatty acids underlies in part the effect of PLA2. Furthermore, modification of the receptor-ligand interaction by changes in the membrane lipid composition may be prevented by ligand occupation of the receptor.     

POSSIBLE RELATIONSHIP BETWEEN ALTERED FATTY ACID COMPOSITION OF SERUM,PLATELETS, AND AORTA AND HYPERTENSION INDUCED BY SUGAR FEEDING IN RATS

To establish a relationship between alterations in fatty acid metabolism, induced by sugar ingestion, and hypertension, we analyzed fatty acid composition of serum, platelets and aorta in rats which had 30% of sugar in their drinking water for 18–20 weeks, and became hypertensive, hypertriglyceridemic and hyperinsulinemic. The fatty acid composition in sugar-fed as compared with that from control rats was as follows: in serum phospholipids, triglycerides and cholesterol ester fractions, palmitic, palmitoleic, oleic and cis-11-eicosadecaenoic acids were present in a higher proportion. In serum phospholipid fraction linoleic and arachidonic acids were decreased and a significant increase was observed in the proportion of dihomo-γ-linolenic acid. In the membrane phospholipids of platelets and aorta, higher proportions of palmitoleic and of oleic acids were observed. Differences in fatty acid composition of phospholipids between sugar-fed and control rats are consistent with altered membrane fluidity. Altered membrane function is a potential mechanism involved hypertension in rats.in sugar-induced     

Effect of felodipine on blood pressure and vascular reactivity in stroke-prone spontaneously hypertensive rats

Isolated tail arteries from stroke-prone spontaneously hypertensive rats (SHRSP), but not from normotensive Wistar-Kyoto rats (WKY), exhibit oscillatory contractions in response to norepinephrine. Previous studies indicate that the mechanism for these oscillations involves altered membrane calcium and/or potassium handling, and that this vascular change is a genetic defect associated with hypertension in SHRSP. The purpose of this experiment was to determine whether treatment of SHRSP with the calcium entry blocker felodipine would alter oscillatory activity. Adult SHRSP and WKY rats were treated orally with felodipine for 8 weeks. Felodipine treatment produced a significant decrease in blood pressure in SHRSP (control SHRSP: 240 +/- 7 mmHg, n = 6; felodipine-treated SHRSP: 164 +/- 8 mmHg, n = 5, P less than 0.05; tail-cuff method). Helically-cut tail artery strips from all rats were mounted in tissue baths for isometric force recording and exposed to norepinephrine (6 x 10(-9) to 6 x 10(-6) mol/l) for 20 min at each concentration. Oscillatory activity was defined as the sum of the magnitudes of all phasic contractions occurring during the final 10 min of norepinephrine incubation. Oscillatory activity was markedly reduced in tail arteries from felodipine-treated SHRSP when compared with control SHRSP. Felodipine also inhibited oscillatory activity when added directly to the tissue bath. It seems, therefore, that felodipine may lower blood pressure in SHRSP, at least in part, by correcting the genetic defect responsible for oscillatory activity.     

Characteristics of early disorders of fatty-acid composition of kidney lipids in spontaneous (hereditary) arterial hypertension

Fatty acid composition of kidney lipids from spontaneously hypertensive Okamoto-Aoki rats (SHR) and normotensive Wistar rats (NR) was investigated two days after birth by gas-liquid chromatography. In SHR kidney phospholipids, as compared to the respective NR values, the content of arachidonic acid (20:4n6) was decreased and the levels of oleic (18:1n9) and docosahexaenoic (22:6n3) acids were increased; in kidney triglycerides, the content of eicosatrionoic acid (20:3n9) and all fatty acids of the linoleic acid series was decreased, except the content of a polyunsaturated long-chain product of linoleic acid metabolism, docosapentaenoic acid (22:5n6) that was increased. These changes may have developed prenatally as a result of genetic peculiarities of SHR.     

Fatty acid binding protein of cardiac muscle in spontaneously hypertensive rats: effect of hypertrophy and its regression

To investigate the relationship between cardiac hypertrophy associated with hypertension, and the alterations in myocardial lipid metabolism, nicardipine (160 mg/kg/day), hydralazine (40 mg/kg/day), and enalapril (30 mg/kg/day) were administered to spontaneously hypertensive rats from 20 to 24 weeks of age. Drug administration significantly suppressed the increases in blood pressure and the ratio of left ventricular weight to body weight. A marked variation in the fatty acid binding capacities of the delipidated, dealbuminated heart cytosol obtained from these animals was observed in the 24-week-old rats (5.40 +/- 0.31 pmol/micrograms protein in non-treated rats; 4.73 +/- 0.34 pmol/mg protein in nicardipine-treated rats; 5.01 +/- 0.34 pmol/mg protein in hydralazine-treated rats; 4.61 +/- 0.26 pmol/mg protein in enalapril-treated rats) as compared to the 20-week-old non-treated rats (3.38 +/- 0.29 pmol/mg protein). The decrease in this capacity in the drug-treated groups closely correlated with the reduction of cardiac mass, suggesting that the factors governing regression may be closely related to those governing fatty acid binding capacity. It appears that fatty acid binding protein may play an important role in the hypertension-associated hypertrophic myocardium.