Renal Na+-K+-ATPase in weanling and adult spontaneously hypertensive rats

The interrelationships among plasma renin activity (PRA, ng AI/ml plasma/hr), aldosterone concentration (ng%), and renal Na+-K+-ATPase activity (mumole PO4/mg protein/hr) were studied in 9 weanling normotensive spontaneously hypertensive rats (SHR), 9 adult hypertensive SHR, and 9 weanling and 9 adult normotensive Wistar-Kyoto rats (WKY). All groups were placed on a normal (0.4% sodium) diet. PRA and plasma aldosterone, measured in samples drawn from the ether-anesthetized rat, were higher in weanling SHR (15.2 +/- 2.0, 37 +/- 4.2) than in WKY. PRA measured in samples collected from a separate group of unanesthetized weanling SHR was also greater than in age-matched WKY. In adult SHR, PRA (6.1 +/- 0.9) and plasma aldosterone (20.0 +/- 2.7) were decreased. During the weanling period Na+-K+-ATPase activity in SHR was not only greater than in age-matched WKY but was also increased compared to adult normotensive and hypertensive rats (137 +/- 9 weanling SHR, 89 +/- 7 weanling WKY, 73 +/- 11 adult SHR, 84 +/- 17 adult WKY). Thus, during the weanling period the renin-angiotensin-aldosterone (R-A-A) system and renal Na+-K+-ATPase activity are activated in SHR. The elevation of Na+-K+-ATPase activity may be due to increased aldosterone levels. It was noted, however, that plasma aldosterone was similar in adult WKY and weanling SHR, while Na+-K+-ATPase activity was higher in SHR. These findings involving R-A-A and renal Na+-K+-ATPase activity prior to the elevation of blood pressure suggest that the kidneys may play a role in the initiation of hypertension in SHR.     

The blood pressure decrease-induced sympathetic discharge following atrial natriuretic factor administration may offset its natriuretic action

Conscious SHR and WKY rats were infused during 7 days with ANF (Arg 101-Tyr 126), 100 ng/hr/rat, by means of miniosmotic pumps and their basal blood pressure (BP), changes in sodium excretion and urinary catecholamines compared with those at the last day of the infusion. The SHR initial BP of 181 +/- 3 mmHg gradually declined to 137 +/- 5 mmHg. No significant change in blood pressure was observed in the ANF-infused WKY group. However, WKY rats exhibited an increased sodium excretion and urinary dopamine/norepinephrine ratio when compared to sham-infused rats. No such differences were observed in SHR. It is suggested that an ANF-induced withdrawal of the renal sympathetic tone permits the manifestation of its natriuretic action in WKY rats. When, however, a BP decrease predominates, as in SHR, this decrease results in a reflex sympathetic discharge with a renal sympathetic activity over-riding the ANF induced natriuresis seen in WKY rats. Secondary sympathetic responses to the ANF-induced BP decrease have to be thus taken into account when a dissociation between the hypotensive and natriuretic action of ANF is observed in vivo.     

Angiotensin restores atrial natriuretic factor-induced decrease of baroreceptor sensitivity in normotensive rats, but not in spontaneously hypertensive rats

The effect of atrial natriuretic factor (ANF) on baroreflex sensitivity was determined in unanesthetized normotensive (Wistar-Kyoto, WKY) or spontaneously hypertensive rats (SHR) during acute hypertensive stimuli (phenylephrine) or hypotensive stimuli (sodium nitroprusside). The i.v. dose of rat ANF [( Ser99,Tyr126]ANF) was 50 ng/min per rat, sufficient to decrease mean arterial blood pressure (ABP) by about 6 mmHg (1 mmHg = 133.3 Pa) in WKY. SHR showed no change in ABP with this ANF dose. During a control infusion of physiological saline, the mean heart rate (HR) response to increases in ABP was -1.30 +/- 0.27 beats/min (bpm)/mmHg in WKY and -0.37 +/- 0.22 in SHR (p less than 0.05). These values were not affected significantly by ANF. However, ANF blunted chronotropic responses to ABP decreases. The control values of the delta HR/delta ABP slope in WKY and SHR were -2.34 +/- 0.57 and -2.01 +/- 0.37 bpm/mmHg, respectively. In the presence of ANF, the slope changed to -0.36 +/- 0.43 (i.e., bradycardia in response to hypotension) in WKY and to +0.20 +/- 0.21 in SHR (p less than 0.005 for the difference from control for both). This ANF-induced loss of baroreflex sensitivity was reversed in WKY by the addition of angiotensin I (sufficient to increase ABP by 5 mmHg in control rats). Angiotensin did not restore baroreflex sensitivity in ANF-infused SHR, and ANF had no effect on the ABP increase caused by angiotensin in either group. The data suggest that ANF does not act on baroreceptor structures directly, but inhibits mechanisms involved in efferent sympathetic activation. Parasympathetic responses do not appear to be compromised.     

Chronic infusion of low doses of atrial natriuretic factor (ANF Arg 101-Tyr 126) reduces blood pressure in conscious SHR without apparent changes in sodium excretion

Conscious SHR and WKY rats were infused during 7 days with synthetic ANF (Arg 101-Tyr 126), 100 ng/hr/rat (35 pmol/hr/rat) by means of miniosmotic pumps. The SHR initial blood pressure of 177 +/- 5 mmHg gradually dropped to 133 +/- 3 and 142 +/- 4 mmHg the last two days of infusion. No significant change in blood pressure was observed in the ANF-infused WKY group. No apparent difference in natriuresis or diuresis was observed in ANF-infused SHR and WKY when compared with non-infused control groups. A slight but significant lower immunoreactive ANF concentration was found in the atria of SHR than in their normotensive controls. No difference in cardiac weight was found between infused and non-infused rats. It is suggested that the hypotensive response observed in SHR and not in WKY is due to a decrease in vascular peripheral resistance. Whether ANF is involved in the development and maintenance of high blood pressure in SHR remains to be elucidated.     

Role of sodium and water excretion in the antihypertensive effect of vasopressin in the spontaneously hypertensive rat.

Mean arterial pressure (mmHg (1 mmHg = 133.322 Pa)), sodium excretion rate (mumol.kg-1.min-1), and urine flow (microL.kg-1.min-1) were measured in conscious unrestrained spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) before, during, and after a 3-h intravenous infusion of arginine vasopressin (20 ng.kg-1.min-1), an equipressor dose of phenylephrine, or an infusion of the vehicle. Cessation of the phenylephrine infusion was associated with a return of arterial pressure to preinfusion control values in both SHR and WKY. Cessation of the vasopressin infusion was also associated with a return of arterial pressure to preinfusion values in WKY. In contrast, in the SHR, arterial pressure fell from a preinfusion control level of 164 +/- 6.2 to 137 +/- 4 mmHg within 1 h of stopping the vasopressin infusion. Five hours after stopping the infusion, pressure was 134 +/- 3 mmHg (29 +/- 5 mmHg below preinfusion levels). Similar to the WKY, cessation of a vasopressin infusion was associated with a return of arterial pressure to preinfusion values in Sprague-Dawley rats. Thus, the failure to observe a hypotensive response in normotensive rats was not a peculiarity of the WKY strain. Sodium excretion rates increased during the infusions of vasopressin to a greater extent in SHR than in WKY. However, the natriuresis induced by phenylephrine was not significantly different from that generated by vasopressin in SHR, and in WKY, the natriuresis was greater for phenylephrine than for vasopressin. Urine output increased to a greater extent during the infusions of phenylephrine in both SHR and WKY than during vasopressin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Body fluids and plasma atrial peptide after its chronic infusion in hypertensive rats

To determine the role of body fluid volume in the chronic hypotensive effect of atrial natriuretic factor (ANF), spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were infused with the peptide (Arg 101-Tyr 126) at a rate of 100 ng/h/rat for 5 days. Blood pressure (BP) was decreased from 176 +/- 4 to 133 +/- 3 mmHg in the SHR group 4 days after ANF infusion was initiated, whereas no changes were observed in ANF-infused WKY animals. Starting 5 days after the infusion began, body fluid measurements revealed no differences in plasma, blood and extracellular fluid volumes or in interstitial spaces. BP and plasma ANF concentrations were determined in another set of experiments before, during and after chronic ANF infusion. BP declined from 169 +/- 3 to 133 +/- 5 mmHg in SHR 5 days after the infusion commenced, but returned to basal values by day 10 or 11. Plasma ANF was significantly higher in SHR than in WKY rats throughout the observation period. However, there were no discernible changes in this parameter in ANF-infused SHR compared to non-infused SHR. A 3-fold rise in plasma ANF was noted in infused WKY rats at day 3 only. It is concluded that the chronic hypotensive effect of ANF in hypertensive animals is not related to changes in either body fluid volume or distribution. Moreover, the finding that chronic ANF infusion reduces BP in SHR without altering its plasma levels suggests a rapid ANF turnover.     

Natriuretic effect of atrial natriuretic peptide in diabetes insipidus rats

Washout of the solute concentration gradient in the renal medullary interstitium has been suggested to play a role in mediating the natriuretic response to atrial natriuretic peptide (ANP). The purpose of this study was to determine the effects of ANP 8-33 on sodium excretion in Brattleboro diabetes insipidus (DI) rats, in which medullary tonicity is known to be decreased as compared to Long-Evans (LE) control rats. Basal urine osmolality (Uosm) was significantly lower in DI rats as compared to LE rats (123 +/- 6 vs 673 +/- 38 mOsm/kg). Infusion of ANP 8-33 at a rate of 4 micrograms/kg/hr for 60 min resulted in a significantly greater increase in UnaV (delta 6.1 +/- 1.2 vs delta 2.9 +/- 0.7 microEq/min) and urine flow (delta 40 +/- 12 vs delta 8 +/- 7 microliter/min) in the LE rats than in the DI rats. The greater natriuresis occurred in the LE rats despite no significant change in Uosm. Fractional lithium reabsorption (an indicator of proximal sodium reabsorption) decreased similarly in both groups. Infusion of ANP had no effect on mean arterial pressure in LE and DI groups. In summary, infusion of ANP in the DI rat resulted in a significant natriuresis, albeit less than in LE rats. The natriuresis in the LE rats occurred despite no significant change in Uosm. These data suggest that mechanisms other than medullary washout are responsible for the natriuretic effects of ANP.     

Spontaneous hypertension is primarily the result of sympathetic overactivity and immunologic dysfunction

Overactivity of the sympathetic nervous system and immunologic dysfunction have been shown to contribute to development and maintenance of hypertension in the Okamoto spontaneously hypertensive rat (SHR). In this study, the combined effects of reduction in sympathetic activity and immunologic manipulation on spontaneous hypertension have been determined. Neonatal SHRs received sham implants or implants of thymic tissue from Wistar donor rats. In addition, the thymus-implanted SHRs underwent bilateral renal denervation when they were 6 weeks old. At the same time, the sham-implanted SHRs underwent sham renal denervation. The denervations or sham operations were repeated when the SHRs were 9, 12, 15, and 18 weeks old. Wistar-Kyoto (WKY) rats also underwent serial sham renal denervations. Tail-cuff pressure measurements indicated that approximately 75% of the chronic hypertension in the SHRs was prevented by the combination of thymic implants and renal denervations. Direct arterial pressure measurements confirmed these results; when the rats were 21 weeks old, mean arterial pressure averaged 177 +/- 5.5 mm Hg in sham-operated SHRs, 134 +/- 2.7 mm Hg in implanted, denervated SHRs, and 121 +/- 2.1 mm Hg in sham-operated WKY rats. These data indicate that overactivity of the sympathetic nervous system and immunologic dysfunction account for the majority of the hypertension in the Okamoto SHR.     

Overexpression of non-functional LAT1/4F2hc in renal proximal tubular epithelial cells from the spontaneous hypertensive rat.

The present study examined the expression of type 1 L-amino acid transporter (LAT1) and its associated glycoprotein 4F2hc in freshly isolated renal proximal tubules and immortalized renal proximal tubular epithelial (PTE) cells from spontaneously hypertensive (SHR) and normotensive (WKY) rats. The study also examined the inward and outward transport of [(14)C]-L-leucine, the preferred substrate of LAT1. The abundance of LAT1 and 4F2hc was greater in SHR than in WKY, both in freshly isolated renal proximal tubules and immortalized renal proximal tubular cells. In the absence of extracellular Na(+) the BCH (2-aminobicyclo(2,2,1)-heptane-2-carboxylic acid)-sensitive [(14)C]-L-leucine uptake in SHR PTE cells was approximately 50% that observed in WKY PTE cells (77+/-4 vs 164+/-7 pmol/mg protein). In the absence of extracellular Na(+) the affinity of the transporter for the substrate in WKY PTE cells was 7.7-fold that in SHR cells, as evidenced by lower K(0.5) values. Gene silencing with a LAT1 siRNA and a 4F2hc siRNA significantly reduced LAT1 and 4F2hc expression, which was accompanied by a marked reduction in Na(+)-independent [(14)C]-L-leucine uptake in both SHR and WKY PTE cells. The spontaneous and L-leucine-stimulated outward transfer of [(14)C]-L-leucine was Na(+)-independent in both SHR and WKY PTE cells. The spontaneous [(14)C]-L-leucine efflux was higher in WKY than in SHR PTE cells and the potency of L-leucine to stimulate [(14)C]-L-leucine efflux in WKY (EC(50) = 9 microM) was greater than in SHR PTE cells (EC(50) = 41 microM). It is concluded that the SHR kidney overexpress LAT1/4F2hc units which display low affinity for L-leucine transport.     

Altered renal sodium handling in spontaneously hypertensive rats (SHR) after hypertonic saline intracerebroventricular injection: role of renal nerves

The mechanism by which blood pressure rises in the SHR strain remains to be elucidated. Also, there is a surprising lack of experimental data on the natriuretic mechanisms induced by intracerebroventricular (ICV) injection of hyperosmotic saline (HoS) in SHR. In normotensive animals ICV injection of HoS causes coordinated responses including natriuresis and inhibition of renal sympathetic nerve activity. In the present study, we hypothesized that presumable blunting of the sympathoinhibitory response to centrally injected HoS may contribute to a lack of suppression of efferent renal nerve outflow in SHR. To test this hypothesis, the present study evaluates the influence of renal denervation after central HoS injection at increasing concentration on urinary sodium handling in SHR compared with age-matched normotensive WKy rats. The study confirmed previous data showing pronounced natriuretic response to centrally HoS stimuli but also demonstrated that the creatinine clearance (C(Cr)) and fractional sodium excretion responses diminished as graded NaCl concentrations were increased in WKy rats but not in SHR. In SHR, increased FE(Na) obtained by central administration of 0.90 M NaCl was produced by increases in proximal (FEP(Na)) and post-proximal fractional urinary sodium rejection without changes in C(Cr), indicating a direct tubular effect. Renal denervation caused significant antinatriuresis by decreased C(Cr) and increased FEP(Na) reabsorption in WKy but not in SHR. This study suggests that natriuresis observed only after higher centrally HoS stimuli with a rightward shift of dose-response curve provides evidence of a down-regulation of target organ responsiveness of periventricular areas of genetic hypertensive rats.     

D(1) dopamine receptor regulation of NHE3 during development in spontaneously hypertensive rats

To determine if the defective interactions among D(1)-like receptors, G proteins, and Na(+)/H(+) exchanger 3 (NHE3) are consequences of hypertension, we studied these interactions in rats, before (2--3 wk) and after (12 wk) the establishment of hypertension. To eliminate the confounding influence of second messenger action on D(1) receptor-NHE3 interaction, studies were performed in renal brush-border membranes (BBM) devoid of cytoplasmic second messengers. NHE3 activity increased with age in Wistar-Kyoto (WKY) rats (3 wk = 1.48 +/- 0.39, n = 13; 12 wk = 2.83 +/- 0.15, n = 16, P < 0.05) but not in spontaneously hypertensive rats (SHRs; 3 wk = 2.52 +/- 0.37, n = 11; 12 wk = 2.81 +/- 0.20, n = 16). D(1) receptor protein tended to decrease, whereas NHE3 protein tended to increase with age in both WKY and SHRs. However, the inhibitory effect of a D(1)-like agonist, SKF-81297, on NHE3 activity increased with age in WKY rats (3 wk = -40.7 +/- 5.3%, n = 10, 12 wk = -58.7 +/- 4.6%, n = 12, P < 0.05) but not in SHRs (3 wk = -27.6 +/- 5.9%, n = 11, 12 wk = -25.1 +/- 3.2%, n = 11). The decreased inhibitory effect of another D(1)-like agonist, fenoldopam, on NHE3 activity in SHRs was not caused by increased activity and binding of G beta gamma to NHE3 as has been reported in young WKY rats. G(s)alpha mediates, in part, the inhibitory effect of D(1)-like agonists on NHE3 activity. In WKY rats, fenoldopam increased G(s)alpha/NHE3 binding to the same extent in 2-wk-old (1.5-fold, n = 4) and adult (1.5-fold, n = 4) rats. In contrast, in SHRs, fenoldopam decreased the amount of G(s)alpha bound to NHE3 in 2-wk-old SHRs and had no effect in 4-wk-old and adult SHRs. These studies indicate that the decreased inhibitory effect of D(1)-like agonists on NHE3 activity in SHRs (compared with WKY rats) precedes the development of hypertension. This may be caused, in part, by a decreased interaction between G(s)alpha and NHE3 in BBM secondary to impaired D(1)-like receptor function.     

Natriuretic and hypotensive effects of brain natriuretic peptide (BNP) in spontaneously hypertensive rats

Effects of four doses (0.1, 0.2, 1.0 and 2.0 nmol/kg) of brain natriuretic peptide (BNP) on natriuresis and blood pressure were investigated in anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). An intravenous injection of 1.0 and 2.0 nmol/kg of BNP caused a significant increase of natriuresis and reduction of blood pressure in SHR and WKY. These effects were essentially identical to the effects of atrial natriuretic peptide (ANP). Remarkable bioactivity elicited by BNP rasises the possibility that BNP has a role in the regulation of blood pressure and water-electrolyte balance. On the other hand, when the effects of BNP on both strains of rats were compared with those of alpha-human ANP reported previously, the hypotensive effect of BNP was less than those of alpha-human ANP only in SHR. It is suggested that BNP might have different bioactivity than that of ANP in SHR.     

Exaggerated natriuresis in experimental hypertension

The exaggerated natriuretic response to intravenous isotonic saline volume expansion in conscious spontaneous hypertensive rats (SHR), compared to normotensive Wistar-Kyoto rats (WKY), is associated with an exaggerated inhibition of renal nerve activity. Following bilateral renal denervation, the natriuresis was significantly attenuated in SHR but unaffected in WKY. Thus, the exaggerated natriuretic response to intravenous isotonic saline in SHR is dependent on their enhanced inhibition of renal nerve activity. Conscious Dahl salt-sensitive rats, on either low or high salt diet, did not exhibit an exaggerated natriuretic response to intravenous isotonic saline volume expansion which may be explained by their known impairment of cardiopulmonary baroreceptor reflex mediated suppression of efferent sympathetic nerve activity during intravenous volume expansion. Conscious hypertensive DOCA-NaCl rats exhibited an exaggerated natriuretic response to oral but not to intravenous isotonic saline volume expansion, suggesting differences in gastrointestinal absorption of isotonic saline. It is concluded that enhanced inhibition of efferent renal sympathetic nerve activity via cardiopulmonary baroreceptor reflex activation contributes to the exaggerated natriuretic response to intravenous isotonic saline volume expansion in certain models of experimental hypertension.     

Sodium homeostasis in transplanted rats with a spontaneously hypertensive rat kidney

Recipients of a kidney from spontaneously hypertensive rats (SHR) but not from normotensive Wistar-Kyoto rats (WKY) develop posttransplantation hypertension. To investigate whether renal sodium retention precedes the development of posttransplantation hypertension in recipients of an SHR kidney on a standard sodium diet (0.6% NaCl), we transplanted SHR and WKY kidneys to SHR x WKY F1 hybrids, measured daily sodium balances during the first 12 days after removal of both native kidneys, and recorded mean arterial pressure (MAP) after 8 wk. Recipients of an SHR kidney (n = 12) retained more sodium than recipients of a WKY kidney (n = 12) (7.3 +/- 10 vs. 4.0 +/- 0.7 mmol, P < 0.05). MAP was 144 +/- 6 mmHg in recipients of an SHR kidney and 106 +/- 5 mmHg in recipients of a WKY kidney (P < 0.01). Modest sodium restriction (0.2% NaCl) in a further group of recipients of an SHR kidney (n = 10) did not prevent posttransplantation hypertension (MAP, 142 +/- 4 mmHg). Urinary endothelin and urodilatin excretion rates were similar in recipients of an SHR and a WKY kidney. Transient excess sodium retention after renal transplantation may contribute to posttransplantation hypertension in recipients of an SHR kidney.     

Intestinal calcium transport in spontaneously hypertensive rats (SHR) and their genetically matched WKY rats

Calcium transport across the basolateral membranes of the enterocyte represents the active step in calcium translocation. This step occurs by two mechanisms, an ATP-dependent pump and a Ca2+/Na+ exchange process. These studies were designed to investigate these two processes in jejunal basolateral membrane vesicles (BLMV) of the spontaneously hypertensive rats (SHR) and their genetically matched controls, Wistar-Kyoto (WKY) rats. The ATP-dependent calcium uptake was stimulated several-fold compared with no ATP condition in both SHR and WKY, but no differences were noted between rate of calcium uptake in SHR and WKY. Kinetics of ATP-dependent calcium uptake at concentrations between 0.01 and 1.0 microM revealed a Vmax of 0.67 +/- 0.03 nmol/mg protein/20 sec and a Km of 0.2 +/- 0.03 microM in SHR and Vmax of 0.69 +/- 0.12 and a Km of 0.32 +/- 0.14 microM in WKY rats. Ca2+/Na+ exchange in jejunal BLMV of SHR and WKY was investigated in two ways. First, sodium was added to the incubation medium (cis-Na+). Second, Ca2+ efflux from BLMV was studied in the presence of extravesicular Na+ (trans-Na+). Both studies suggest a decreased exchange of calcium and Na+. Kinetic parameters of Na(+)-dependent Ca2+ uptake at concentrations between 0.01 and 1.0 microM exhibited Vmax of 0.05 +/- 0.01 nanmol/mg protein/5 sec and a Km of 0.21 +/- 0.13 microM in SHR and Vmax of 0.11 +/- 0.02 nanmol/mg protein/5 sec and a Km of 0.09 +/- 0.05 in WKY, respectively. These results confirm that the intestinal BLMV of SHR and WKY rats have two mechanisms for calcium extrusion, an ATP-dependent Ca2+ transport process and a Na+/Ca2+ exchange process. The ATP-dependent process appears to be functional in SHR; however, the Ca2+/Na+ exchange mechanism appears to have a marked decrease in its maximal capacity. These findings suggest that calcium extrusion via Ca2+/Na+ is impaired in the SHR, which may lead to an increase in intracellular calcium concentration. These findings may have relevance to the development of hypertension.     

Na-dependent changes in intracellular Ca in spontaneously hypertensive rat hearts.

To determine whether Na/Ca exchange is altered in primary hypertension, Na-dependent changes in intracellular Ca, ([Ca]i), were measured in isolated perfused hearts from Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Intracellular Na, (Nai, mEq/kg dry wt), and [Ca]i were measured by NMR spectroscopy. Control [Ca]i was less in WKY than SHR (176 +/- 18 vs 253 +/- 21 nmol/l; mean +/- S.E., P < 0.05), whereas Nai was not significantly different. One explanation for this is that net Na/Ca exchange flux is decreased in SHR. If this hypothesis is correct, the rate of Ca uptake in SHR should be less than WKY when Na/Ca exchange is reversed by decreasing the transmembrane Na gradient. The Na gradient was reduced by decreasing extracellular Na, ([Na]o) and/or by increasing [Na]i. To increase [Na]i, Na uptake was stimulated by acidification while Na extrusion by Na/K ATPase was inhibited by K-free perfusion. Seventeen minutes after acidification, Nai had increased but was not significantly different in SHR and WKY (18.0 +/- 2.3 to 57.4 +/- 7.6 vs 20.3 +/- 0.6 to 66.5 +/- 4.8 mEq/kg dry wt, respectively). Yet [Ca]i was greater in WKY than SHR (1768 +/- 142 vs 1201 +/- 90 nmol/l; P < 0.05). [Ca]i was also measured after decreasing [Na]o from 141 to 30 mmol/l. Fifteen minutes after reducing [Na]o, [Ca]i was greater in WKY than SHR (833 +/- 119 vs 425 +/- 94 nmol/l; P < 0.05). Thus for both protocols, decreasing the transmembrane Na gradient led to increased [Ca]i in both SHR and WKY, but less increase in SHR. The results are consistent with the hypothesis that Na/Ca exchange activity is less in SHR than WKY myocardium.     

Liver oleic acid biogenesis is impaired during the prehypertensive period in the spontaneously hypertensive rat

In the present study, we have investigated the liver microsomal stearic acid delta9 desaturation, and the fatty acid composition of liver microsomal total lipids in 10- and 30-day-old spontaneously hypertensive rats (SHRs), compared to the normotensive Wistar Kyoto (WKY) control rats. So as to avoid any influence related to the diet, the composition of the milk being different in SHR and WKY strains, the pups were suckled by adoptive normotensive female Wistar. After weaning, the 30-day-old rats were fed a standard commercial diet and then killed. Our results show lower liver microsomal delta9 desaturase activities in the 10- and 30-day-old SHR versus the WKY of the same age. The fatty acid composition of the SHR liver microsomal total lipids are not in agreement with the changes in the delta9 desaturase activities at the two studied ages. This phenomenon depends not only on desaturation/elongation but also on other interacting aspects of lipid metabolism including oxidation, substrate availability, acyl exchange, and eicosanoid synthesis, as well as hormonal status.     

Natriuretic effect of digoxin-like immunoreactive substance on dog kidney

We previously reported that digoxin-like immunoreactive substance (DLIS) was found only in the blood of those dialysis patients who were hypertensive and had high systemic vascular resistance. In order to determine whether the DLIS was a marker for the natriuretic hormone, renal infusion studies were carried out in anesthetized dogs. When ultrafiltrates from patients with high blood DLIS levels were infused into the renal artery of one kidney there was a significant increase in the fractional excretion of sodium (FE Na) from its baseline value. Further, the FE Na of these kidneys were significantly higher than the FE Na noted for the contralateral kidneys which were simultaneously infused with ultrafiltrates obtained from dialysis patients lacking DLIS activity in their blood. We conclude that the DLIS is or represents a marker for natriuretic hormone. Since the natriuresis noted was independent of renal plasma flow and glomerular filtration rate and since the fractional excretion of potassium was not influenced by the infusion, we believe that DLIS is different from atrial natriuretic factor.     

Na+/H+ exchange in erythrocytes of spontaneously hypertensive rats: a study in F2 SHR x WKY hybrids.

The rate of proton gradient-induced Na+/H+ exchange in the erythrocytes of SHR was increased by 50-60% as compared to WKY animals. No significant correlation between Na+/H+ exchange and blood pressure was revealed in F2 hybrids of SHR and WKY rats. Na+/H+ exchange rate in the erythrocytes of F2 SHR x WKY hybrids was twice as high as in SHR and three times higher than in WKY rats.     

Decreased content in left atrium and increased plasma concentration of atrial natriuretic polypeptide in spontaneously hypertensive rats (SHR) and SHR stroke-prone

The atrial contents and concentrations, and the plasma concentrations of atrial natriuretic polypeptide (ANP) in spontaneously hypertensive rats (SHR) and SHR stroke-prone (SHRSP) were measured and compared with those of age-matched Wistar Kyoto rats (WKY) using a specific radioimmunoassay (RIA) for alpha-rat ANP (alpha-rANP). The contents of alpha-rANP-LI in the atria of SHR (19.0 +/- 0.9 micrograms, mean +/- SEM) and SHRSP (19.3 +/- 0.6 micrograms) were significantly lower than that of WKY (22.8 +/- 1.4 micrograms) (p less than 0.05). The atrial concentration of alpha-rANP-LI was also significantly lower in SHR (248.2 +/- 11.3 ng/mg, p less than 0.05) and tended to be lower in SHRSP (272.2 +/- 12.4 ng/mg) than that of WKY (300.0 +/- 14.2 ng/mg). Furthermore, the concentrations in the left auricles of SHR and SHRSP were significantly lower than that of WKY (p less than 0.01 and p less than 0.05, respectively). In contrast, no significant difference was observed in the alpha-rANP-LI concentrations in the right auricles of WKY, SHR and SHRSP. Gel filtration studies coupled with RIA showed that gel filtration profiles of the extracts from the right and left auricles of WKY, SHR and SHRSP were essentially identical. The plasma alpha-rANP-LI levels in SHR (260 +/- 34 pg/ml) and SHRSP (319 +/- 19 pg/ml) were significantly higher than that in WKY (170 +/- 17 pg/ml) (p less than 0.05 and p less than 0.01, respectively). These results suggest that the secretion of ANP from the heart is increased in SHR and SHRSP compared with WKY.