Effects of chronic salt loading on plasma atrial natriuretic peptide (ANP) in the spontaneously hypertensive rat

Plasma concentrations of immunoreactive atrial natriuretic peptide (ANP) was measured in spontaneously hypertensive rats (SHR) during chronic salt loading (1.5% NaCl in drinking water). During the 3-week experimental period mean arterial blood pressure, heart rate, urinary sodium excretion and body weight was assessed in salt-loaded as well as in control rats. The sodium excretion was more than 10-fold increased in the rats on the high salt diet. The plasma ANP concentration was significantly increased only 24 h after the start of the high salt intake. Thereafter plasma ANP concentrations were not significantly different from values obtained in control rats. The blood pressure was significantly increased after 3 weeks on the high salt diet. At the end of the 3-week experimental period the rats were subjected to a 10 and 20% acute volume expansion with homologous whole blood. During this intervention the increase in plasma ANP concentrations was blunted in the high salt rats compared to the control group. It is concluded that during chronic salt loading in SHR there is an initial rise in plasma ANP levels and that other hormonal and neuronal systems are more important in the long term maintenance of fluid and electrolyte balance.     

Effects of calcium supplementation and deoxycorticosterone on plasma atrial natriuretic peptide and electrolyte excretion in spontaneously hypertensive rats.

The effects of calcium and the mineralocorticoid deoxycorticosterone (DOC) on blood pressure were studied in four groups of spontaneously hypertensive rats (SHR): (1) control; (2) calcium; (3) deoxycorticosterone and; (4) deoxycorticosterone + calcium. Calcium was given as 1.5% calcium chloride in drinking fluid and deoxycorticosterone by weekly subcutaneous injections (25 mg kg-1). During the nine weeks of treatment the increase in systolic blood pressure was enhanced in the deoxycorticosterone and attenuated in the calcium group, whereas the deoxycorticosterone + calcium group did not deviate from control. Total plasma calcium was elevated in the calcium group. Plasma concentrations of sodium and atrial natriuretic peptide (ANP) were increased by deoxycorticosterone while neither of the calcium-treated groups differed from control in these respects. Urinary excretions of calcium and sodium were increased in both groups receiving calcium, and also the deoxycorticosterone group excreted more calcium into urine than the control. Adrenergic nerve density in a section of the mesenteric artery and the urinary excretion of noradrenaline and adrenaline were similar in all study groups. The results indicate that calcium supplementation can attenuate the development of hypertension and prevent the deoxycorticosterone-induced blood pressure rise in SHR, possibly by influencing sodium metabolism as seen in increased natriuresis, and by preventing the actions of deoxycorticosterone on sodium balance.     

Effects of calcium supplementation and deoxycorticosterone on plasma atrial natriuretic peptide and electrolyte excretion in spontaneously hypertensive rats

The effects of calcium and the mineralocorticoid deoxycorticosterone (DOC) on blood pressure were studied in four groups of spontaneously hypertensive rats (SHR): (1) control; (2) calcium; (3) deoxycorticosterone and; (4) deoxycorticosterone + calcium. Calcium was given as 1.5% calcium chloride in drinking fluid and deoxycorticosterone by weekly subcutaneous injections (25 mg kg^-1). During the nine weeks of treatment the increase in systolic blood pressure was enhanced in the deoxycorticosterone and attenuated in the calcium group, whereas the deoxycorticosterone + calcium group did not deviate from control. Total plasma calcium was elevated in the calcium group. Plasma concentrations of sodium and atrial natriuretic peptide (ANP) were increased by deoxycorticosterone while neither of the calcium-treated groups differed from control in these respects. Urinary excretions of calcium and sodium were increased in both groups receiving calcium, and also the deoxycorticosterone group excreted more calcium into urine than the control. Adrenergic nerve density in a section of the mesenteric artery and the urinary excretion of noradrenaline and adrenaline were similar in all study groups. The results indicate that calcium supplementation can attenuate the development of hypertension and prevent the deoxycorticosterone-induced blood pressure rise in SHR, possibly by influencing sodium metabolism as seen in increased natriuresis, and by preventing the actions of deoxycorticosterone on sodium balance.     

Renal dopamine and noradrenaline excretion during CNS-induced natriuresis in spontaneously hypertensive rats: influence of dietary sodium

Abnormalities in dopamine (DA) and noradrenaline (NA) activities and sodium handling may be involved in the pathogenesis of hypertension. The present study was designed to investigate whether any differences exist between normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in urinary excretion of DA, NA and sodium after 15 weeks on a low, medium or high sodium diet and during a subsequent elevation of the cerebroventricular fluid sodium concentration (CNS-induced natriuresis). Seven features were noted: (1) Basal sodium and DA excretion after the diet regimen was correlated to the dietary sodium content in both strains, except that sodium and DA excretion in SHR showed no further increase after the high sodium diet over and above that after medium sodium diet. (2) For any given sodium diet, SHR excreted more DA and NA as compared with WKY. (3) Blood pressure in SHR, as opposed to that in WKY, was higher after medium and high sodium diet than after low sodium diet. (4) During CNS-induced natriuresis NA excretion decreased or remained unchanged in WKY, but increased in SHR. (5) The DA/NA excretion ratio during CNS-induced natriuresis increased in WKY while decreased in SHR, which would not favour a natriuretic/vasodilatory response in the latter. (6) The ability of SHR to respond with CNS-induced natriuresis was attenuated after high sodium diet. (7) The magnitude of CNS-induced natriuresis was in both strains correlated to the sodium diet; the higher the dietary sodium content, the greater the natriuretic response. In conclusion, the study shows some clear differences in the catecholamine and sodium handling between WKY and SHR which may be involved in the pathogenesis of hypertension in SHR. Furthermore, increased sodium in the diet sensitizes the brain and kidney to increase the ability to respond with natriuresis for a given sodium stimulus.     

Renal dopamine and noradrenaline excretion during CNS‐induced natriuresis in spontaneously hypertensive rats: influence of dietary sodium

Abnormalities in dopamine (DA) and noradrenaline (NA) activities and sodium handling may be involved in the pathogenesis of hypertension. The present study was designed to investigate whether any differences exist between normotensive Wistar–Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in urinary excretion of DA, NA and sodium after 15 weeks on a low, medium or high sodium diet and during a subsequent elevation of the cerebroventricular fluid sodium concentration (CNS‐induced natriuresis). Seven features were noted: (1) Basal sodium and DA excretion after the diet regimen was correlated to the dietary sodium content in both strains, except that sodium and DA excretion in SHR showed no further increase after the high sodium diet over and above that after medium sodium diet. (2) For any given sodium diet, SHR excreted more DA and NA as compared with WKY. (3) Blood pressure in SHR, as opposed to that in WKY, was higher after medium and high sodium diet than after low sodium diet. (4) During CNS‐induced natriuresis NA excretion decreased or remained unchanged in WKY, but increased in SHR. (5) The DA/NA excretion ratio during CNS‐induced natriuresis increased in WKY while decreased in SHR, which would not favour a natriuretic/vasodilatory response in the latter. (6) The ability of SHR to respond with CNS‐induced natriuresis was attenuated after high sodium diet. (7) The magnitude of CNS‐induced natriuresis was in both strains correlated to the sodium diet; the higher the dietary sodium content, the greater the natriuretic response. In conclusion, the study shows some clear differences in the catecholamine and sodium handling between WKY and SHR which may be involved in the pathogenesis of hypertension in SHR. Furthermore, increased sodium in the diet sensitizes the brain and kidney to increase the ability to respond with natriuresis for a given sodium stimulus.     

Age-related changes in the renal dopaminergic system and expression of renal amino acid transporters in WKY and SHR rats

This study examined age-related changes in renal dopaminergic activity and expression of amino acid transporters potentially involved in renal tubular uptake of l-DOPA in Wistar Kyoto (WKY) and spontaneously hypertensive rats. Aging (from 13 to 91 weeks) was accompanied by increases in systolic blood pressure (SBP) in both WKY and SHR. The sum of urinary dopamine and DOPAC and the urinary dopamine/l-DOPA ratio were increased in aged SHR but not in aged WKY. The urinary dopamine/renal delivery of l-DOPA ratio was increased in both rat strains with aging. LAT2 abundance was increased in aged WKY and SHR. The expression of 4F2hc was markedly elevated in aged SHR but not in aged WKY. ASCT2 was upregulated in both aged WKY and SHR. Plasma aldosterone levels and urinary noradrenaline levels were increased in aged WKY and SHR though levels of both entities were more elevated in aged SHR. Activation of the renal dopaminergic system is more pronounced in aged SHR than in aged WKY and is associated with an upregulation of renal cortical ASCT2 in WKY and of LAT2/4F2hc and ASCT2 in SHR. This activation may be the consequence of a counter-regulatory mechanism for stimuli leading to sodium reabsorption.     

Renal interaction between sympathetic activity and ANP in rats with chronic ischaemic heart failure

The diuretic and natriuretic effects of r-alpha-ANP (99-126) were investigated in rats with chronic ischaemic heart failure (IHF) produced by left coronary artery ligation. The plasma concentration of immunoreactive ANP (IrANP) was significantly higher, 91.8 +/- 16.0 pm in the IHF rats compared to 31.0 +/- 4.9 pm in sham-operated controls. In the control rats, ANP infusion (0.25-1.0 micrograms kg 1 mm 1) increased urine flow rate (V) and urinary sodium (UNa V) excretion. At the highest dose level, both V and UNa V were increased approximately fivefold. The diuresis and natriuresis seen in the control group after the infusion of ANP were blunted in the IHF rats. A bilateral surgical renal denervation in the IHF rats did not alter the renal dopamine levels, but induced a significant decrease in renal noradrenaline content, and almost completely restored the renal responsiveness to the ANP infusions. We conclude that renal denervation reversed the blunted renal excretory response to ANP in IHF rats. Thus, in experimental IHF, there seems to be a functional antagonism between efferent renal sympathetic nerve activity and ANP.     

Renal and hormonal responses to atrial natriuretic peptide infusions in goats on high and low sodium intake

Synthetic atrial natriuretic peptide (ANP) was infused intravenously (1 microgram min-1; 60 min) in five goats during two series of experiments. For at least 4 weeks before the ANP infusions the goats received either no salt supplementation (= low sodium diet), or were given 16 g NaCl mixed with the food each day (Na = 274 mmol day-1; high sodium intake). The goats were changed between the treatments at random. ANP infusions caused diuresis, natriuresis and haemoconcentration during both diets. The urinary Na excretion increased about four-fold during the high sodium intake, and about 10 times during the low sodium intake. The urinary K excretion increased significantly during the low sodium diet, but decreased slightly during the high sodium intake. During both diets the K excretion became significantly lowered after the infusions. The mean glomerular filtration rate (GFR) was generally lower during the low sodium diet, but increased significantly during ANP infusions on both diets. The GFR returned to baseline immediately after the infusions, in contrast to urine flow and urinary Na excretion. Renal free water clearance increased slightly at the end of the infusion during the low sodium diet, but did not change during the high salt diet. Plasma renin activity (PRA) and plasma aldosterone concentration fell during ANP infusions in goats on the low sodium intake, but did not change significantly during the high sodium diet. These results indicate that the diuresis and natriuresis observed during intravenous ANP infusions in goats are mainly due to increased GFR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Body composition, intraerythrocyte sodium content, volume regulation and blood pressure during moderate sodium restriction in hypertensive men

Eleven moderately obese middle-aged male outpatients with untreated mild hypertension reduced their sodium intake by about 120 mmol per day during 4-6 weeks. Diastolic blood pressure was then significantly reduced in comparison with a matched control group. The reduction of urinary sodium excretion was significantly correlated to the change in mean arterial pressure. Mean body mass showed a small significant decrease, although there were no significant changes in total body water or body fat as determined from measurements of 40K and tritiated water. Nor did mean extracellular water or plasma volume (Evan's blue) show any significant change. The decrease in urinary sodium excretion was associated with increases in plasma renin activity and urinary aldosterone excretion, while a sympathetic nervous natriuretic index (urinary dopamine to noradrenaline excretion ratio) decreased. The low sodium diet period was followed by a period of energy reduction as well as sodium restriction for 15 weeks. Mean body mass was then reduced by about 8 kg. The systolic but not the diastolic blood pressure showed a significant decrease. The intraerythrocyte content of water, sodium and potassium did not change significantly during any of the diet periods. We conclude that moderate sodium restriction lowered the blood pressure and affected the renin-aldosterone and sympathetic nervous system to retain sodium which might explain the constancy of the plasma volume.     

Effects of the calcium antagonist felodipine on the sympathetic and renin-angiotensin-aldosterone systems in essential hypertension

Studies were performed in 10 male patients with untreated essential hypertension, WHO grade I-II, aged 25-62 years, to explore the acute (single dose) and long-term (8 weeks) effects of felodipine on sympathetic activity--evaluated by plasma and urinary catecholamines--as related to blood pressure, heart rate and the activity in the renin-angiotensin-aldosterone system. The patients were hospitalized for 8 (acute) and 6 (long-term) days and were maintained on a standardized daily intake of sodium (150 mmol), potassium (75 mmol) and water (2,500 ml). Acute felodipine administration (10 mg) significantly reduced blood pressure and increased heart rate. Plasma and urinary noradrenaline, plasma renin activity and angiotensin II increased, whereas plasma and urinary adrenaline, dopamine, aldosterone and plasma vasopressin were unaltered. Long-term felodipine treatment, 10 mg twice daily, reduced blood pressure to a similar extent as acute felodipine administration, but heart rate was not significantly changed. Plasma noradrenaline 3 and 12 hours after the last dose and urinary noradrenaline were increased, whereas plasma and urinary adrenaline and dopamine were unchanged. Plasma renin activity and angiotensin II were increased 3 hours, but unchanged 12 hours after the last dose. Plasma aldosterone was unchanged but urinary aldosterone increased. Plasma vasopressin was unchanged. The changes in plasma noradrenaline as related to blood pressure, heart rate, plasma renin activity and angiotensin II during long-term felodipine treatment may reflect decreased cardiac and renal beta-adrenoceptor-mediated responses. Increased renal clearance of aldosterone could partly explain the unaltered plasma aldosterone level in spite of increased plasma angiotensin II following long-term felodipine treatment.     

Haemodynamics and plasma ANP (atrial natriuretic peptide) after acute blood volume expansion in normotensive and spontaneously hypertensive rats

Atrial natriuretic peptide (ANP) was measured in plasma during acute volume load in conscious, spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. During basal conditions immunoreactive ANP were similar in the SHR (630 +/- 56 pmoles l-1) and the WKY (657 +/- 114 pmoles l-1) groups. An acute 10% and 20% whole blood volume expansion resulted in a linear increase in immunoreactive plasma ANP in the WKY. In the SHR the increase in plasma ANP was attenuated during the 20% volume load. During the 10% and 20% volume load central venous pressure (CVP), central blood volume (CBV) and cardiac output increased relatively more in the SHR compared with the WKY group. In contrast, the increase in peripheral blood volume (PBV) and decrease in heart rate (HR) was attenuated in the SH rats. In the SHR group there was a shift of the ANP vs. CVP and ANP vs. CBV curves to the right compared with the WKY. We conclude that acute volume loading is a potent stimulus for ANP release in WKY as well as SHR. However, in the SHR, ANP release was blunted in spite of the increased centralization of the volume load in this rat strain. Thus, the decreased responsiveness of the ANP hormonal system may contribute to the development and maintenance of hypertension in this genetic form of hypertension.     

Pathophysiologic role of natriuretic peptides

To evaluate the pathophysiologic role of atrial natriuretic peptide (ANP) in hypertension, hemodynamic effects of human ANP and antiserum against rat ANP were investigated in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Intravenous administration of human ANP caused greater hypotension associated with a decrease of cardiac output in SHR than in WKY, which suggests that SHR have enhanced responsiveness to exogenous ANP. The antiserum increased blood pressure and cardiac output, with the latter being significantly greater in SHR than in WKY. These results suggest that endogenous ANP counteract, in part, the maintenance of hypertension. In addition, hemodynamic and renal excretory effects of brain natriuretic peptide (BNP), a novel natriuretic peptide identified from porcine, were studied in SHR and WKY. BNP caused marked natriuresis and hypotension in a dose-dependent fashion, as observed with ANP. Not only ANP but also BNP may have a role in the regulation of blood pressure and water-electrolyte balance.     

Influence of water and sodium diuresis and furosemide on urinary excretion of vitamin B(6), oxalic acid and vitamin C in chronic renal failure

Urinary excretion of vitamin B(6), oxalic acid and vitamin C was investigated in 15 healthy subjects during maximal water diuresis and in the group of 12 patients in polyuric stage of chronic renal failure without dialysis treatment receiving a diet containing high sodium chloride (15g/day). Urinary excretions of the same parameters were investigated in another group of 15 patients in polyuric stage of chronic renal failure without dialysis treatment after i.v. administration of 20 mg furosemide. Urinary excretion of vitamin B(6), oxalic acid and vitamin C significantly increased during maximal water diuresis while during high intake of sodium chloride the urinary excretions of these substances were not affected. The results suggest that urinary excretion of vitamin B(6), oxalic acid and vitamin C depends on the urinary excretion of water. Intravenous administration of 20 mg furosemide led to an increase of urinary excretion of vitamin B(6), oxalic acid and vitamin C in patients with chronic renal failure. The increased urinary excretion of vitamin B(6) and vitamin C is a new negative side effect of furosemide and increased urinary excretion of oxalic acid is a new positive side effect in patients with chronic renal failure.     

The effect of sodium depletion and potassium supplementation on vasopressin, renin and catecholamines in hypertensive men

Seventeen 50-year-old hypertensive men (157 +/- 4/110 +/- 2 mmHg, mean +/- SE) were given low sodium diet for one week, which was supplemented with potassium the following week. The urinary Na+/K+ excretion ratio changed from 2:1 to 1:5 and 1:12, respectively, during dietary intervention. Arterial plasma vasopressin decreased by 3.4 +/- 1.7 ng/l (0.05 less than p less than 0.10) and urinary excretion of vasopressin was reduced by nearly 50% (p less than 0.001) during sodium depletion, while plasma noradrenaline increased by 38% (p less than 0.001) and plasma dopamine showed an increase by 58% (p less than 0.001). Plasma renin concentration increased four-fold during sodium depletion (p less than 0.001). With combined salt depletion and potassium supplementation, arterial plasma vasopressin decreased by 9.5 +/- 4.0 ng/l (p less than 0.05) compared to control. Urinary excretion of vasopressin together with plasma noradrenaline and dopamine were unchanged during the second week. The reduction of blood pressure was most marked during the first week (143 +/- 3/103 +/- 2 mmHg, p less than 0.05), but continued to fall also during the second week. Thus, during sodium restriction in middle-aged hypertensive men, blood pressure reduction occurs concomitantly with inhibited vasopressin release, despite enhanced renin and catecholamine release. Potassium supplementation during sodium restriction induces only minor changes in these variables.     

Intrarenal dopamine coordinates the effect of antinatriuretic and natriuretic factors

The precision by which sodium balance is regulated suggests an intricate interaction between modulatory factors released from intra- and extrarenal sources. Intrarenally produced dopamine has a central role in this interactive network. Dopamine, produced in renal tubular cells acts as an autocrine and paracrine factor to inhibit the activity of Na+,K+-ATPase as well as of a number of sodium influx pathways. The natriuretic effect of dopamine is most prominent under high salt diet. The antinatriuretic effects of noradrenaline, acting on alpha-adrenoceptors and angiotensin II are opposed by dopamine as well as by atrial natriuretic peptide (ANP). Several lines of evidence have suggested that ANP acts via the renal dopamine system and recent studies from our laboratory have shown that this effect is attributed to recruitment of silent D1 receptors from the interior of the cell towards the plasma membrane. Taken together, the observations suggest that dopamine coordinates the effects of antinatriuretic and natriuretic factors and indicate that an intact renal dopamine system is of major importance for the maintenance of sodium homeostasis and normal blood pressure.     

A “Western Diet” promotes symptoms of hepatic steatosis in spontaneously hypertensive rats

Systemic hypertension, characterized by elevated blood pressure ≥140/90 mm Hg, is a major modifiable risk factor for cardiovascular disease. Hypertension also associates with non‐alcoholic fatty liver disease (NAFLD), which is becoming common due to a modern diet and lifestyle. The aim of the present study was to examine whether a high‐fat "Western" diet had effects on hypertension and associated NAFLD. Normotensive Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were placed on a normal chow or high‐fat diet for 8 weeks; blood pressure was measured fortnightly and body weight recorded weekly. As expected, SHR had elevated blood pressure compared to WKY. Diet did not influence blood pressure. Compared to SHR, WKY rats gained more weight, associating with increased white adipose tissue weight. Normotensive rats also had higher plasma cholesterol and triglycerides in response to a “Western” diet, with no changes in plasma glucose levels. Neither strain developed atherosclerosis. Interestingly, high‐fat diet‐fed SHR had increased liver weight, associating with a significant level of hepatic lipid accumulation not observed in WKY. Further, they exhibited hepatocellular ballooning and increased hepatic inflammation, indicative of steatohepatitis. These findings suggest that a high‐fat “Western” diet promotes features of NAFLD in SHR, but not WKY rats. Importantly, the high‐fat diet had no effect on blood pressure.     

Hemodynamic,renal, and hormonal responses to changes in dietary potassium in normotensive and hypertensive man: Long-term antihypertensive effect of potassium supplementation in essential hypertension

Summary The hemodynamic, hormonal, and renal responses to alterations in dietary potassium were studied in normotensive and hypertensive subjects. In a short-term study, nine normotensive and nine hypertensive young men received a normal diet and low potassium, high potassium, and high potassium/low sodium diets for 1 week, each. The long-term effect of potassium supplementation (normal diet plus 96 mmol KCl/d for 8 weeks) was evaluated in 17 patients with essential hypertension. Blood pressure did not change significantly during short-term alterations of potassium intake but decreased during long-term supplementation (from 152.2±3.5/99.6±1.9 mm Hg to 137.4±2.9/89.1±1.4 mm Hg). High dietary potassium induced a significant but transient natriuresis. Plasma potassium concentration was increased during long- but not during short-term high potassium intake. In contrast to plasma renin activity (PRA) and aldosterone, urinary kallikrein was consistently stimulated during long-term potassium supplementation. The plasma concentrations of adrenaline and noradrenaline were significantly higher in hypertensive than in normotensive subjects and were not markedly altered by the dietary changes. It is concluded that long- but not short-term potassium supplementation lowers blood pressure in patients with essential hypertension. The antihypertensive effect may be mediated by potassium-induced natriuresis, by a stimulation of Na-K-ATPase secondary to increased plasma potassium levels, and/or by a modulation of the renin-angiotensin-aldosterone, kallikrein-kinin, and sympathetic nervous systems.Abbreviations MAP mean arterial pressure - Na-K-ATPase sodium-potassium ATPase - PRA plasma renin activity The study was supported in part by the Ministerium für Wissenschaft und Forschung, Nordrhein-Westfalen (FA-92/14)     

Sodium balance during development of hypertension in the spontaneously hypertensive rat (SHR)

Sodium balance was studied in 7 and 16 week old male spontaneously hypertensive rats (SHR), in matched normotensive Wistar rats (NCR) and in Wistar Kyoto rats (WKR). The animals were placed in metabolic cages and given diets with either normal sodium content (5.35 mmol sodium/100 g food) or with a sodium content 3 or 10 times the normal. Whether on normal or increased sodium diet we did not observe any increased sodium retention in either SHR age group. However, in both SHR groups urinary sodium excretion was significantly decreased, while faecal sodium excretion was correspondingly increased compared with the controls. This shift of sodium excretion from kidneys to gastrointestinal tract in SHR did not reflect any ‘primary’ inability of the SHR kidneys to excrete sufficient sodium amounts since on high sodium diet they excreted the increased sodium load as readily as the normotensive controls. The present results do not support the concept that a primary renal retention of sodium and water should be of pathogenetic importance for the SHR variant of primary hypertension.     

Temporal characteristics of cardiomyocyte hypertrophy in the spontaneously hypertensive rat.

BACKGROUND: The spontaneously hypertensive rat (SHR) is frequently used as model of cardiovascular disease, with considerable disparity in reported parameters of hypertrophy. The aim of this study was to assess the temporal changes occurring during the development and progression of cardiomyocyte hypertrophy in SHR, subsequent to pressure overload, compared to changes associated with normal aging using the normotensive Wistar-Kyoto (WKY) rat. METHODS: Ventricular cardiomyocytes were isolated from rats at 8, 12, 16, 20 and 24 weeks, and parameters of hypertrophy (cell dimensions, protein mass, de novo protein synthesis, and gene expression) and function (contraction and hypertrophic responsiveness in vitro) were assessed. RESULTS: Hypertension was evident at > or =7 weeks in SHRs. Heart:body mass ratio, cardiomyocyte protein mass and width were elevated (P<.05) in SHRs at 16-20 weeks compared to WKYs. In SHRs compared to WKYs at 16 weeks, there was a transient increase (P<.05) in protein synthesis, enhanced hypertrophic responsiveness to phorbol-12-myristate-13-acetate, and induced hypertrophic responsiveness to isoprenaline. Skeletal-alpha-actin mRNA was detected in SHR but not WKY cells at all ages. ANP mRNA was lower in SHR than in WKY cells at 8-20, but progressively increased (P<.05) from 12 to 24 weeks within SHRs. Contractile function increased (P<.05) at 20 weeks in SHR compared to WKY rats. CONCLUSION: Structural and functional changes occurring at the cellular level in the myocardium of SHR follow a distinct pattern, such that pressure overload was initially accompanied by expressional changes (8-12 weeks), followed by active hypertrophic growth and enhanced function (16-20 weeks), which subsequently decelerated as stable compensation was attained.