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.     

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.     

Reduction of blood pressure and increased diuresis and natriuresis during chronic infusion of atrial natriuretic factor (ANF Arg 101-Tyr 126) in conscious one-kidney, one-clip hypertensive rats

Conscious one-kidney, one-clip hypertensive rats and their normotensive controls were infused during 7 days with synthetic ANF (Arg 101-Tyr 126) at 100 ng/hr/rat (35 pmol/hr/rat) by means of osmotic minipumps. The basal blood pressure of 193 +/- 6 mmHg gradually declined to 145 +/- 6 mmHg at day 4 after the infusion was started. No changes in blood pressure were observed in ANF-infused normotensive rats. A significantly higher diuresis and natriuresis was observed in ANF-infused hypertensive rats when compared to the non-treated hypertensive group. No such changes were observed in ANF-treated normotensive animals. No differences in PRA were seen in any group. Atrial immunoreactive ANF was significantly lower in one-kidney, one-clip rats than in the normotensive animals, but whether this is the reflection of an increased release in the circulation remains to be elucidated. It is suggested that the hypotensive response of one-kidney, one-clip animals to ANF may be secondary to a dual mechanism, vasodilatation and volume depletion.     

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)     

Effect of chronic infusion of synthetic atrial natriuretic factor (ANF 8-33) in conscious two-kidney, one-clip hypertensive rats

Conscious two-kidney, one-clip hypertensive rats were chronically infused during 7 days with synthetic ANF (8-33) (1 microgram/hr/rat) by means of osmotic minipumps. The initial blood pressure of 183 +/- 4 mmHg gradually decreased to 116 +/- 5 mmHg the last 2 days of infusion. Pressure diuresis returned to normal and pressure natriuresis was attenuated. PRA was significantly lower (1.81 +/- 0.41 AI ng/ml/hr) than in not treated hypertensive rats (8.56 +/- 3.75 AI ng/ml/hr). A partial regression in cardiac hypertrophy was observed in the treated group. We suggest that the hypotensive response to ANF may be mainly due to vasodilatation, but the possibility that the decrease in PRA may play a partial role in lowering blood pressure, cannot be excluded.     

The effect of prolonged infusion and withdrawal of angiotensin II in the spontaneously hypertensive rat

In spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto controls (WKY), prolonged intravenous administration of angiotensin II (AII, 0.2 microgram X kg-1 X min-1 for 3h) resulted in similar increases in arterial blood pressure. Heart rate decreased in WKY and increased in SHR. At the end of the infusion, blood pressure dropped substantially in SHR, but not in WKY: at 5 h after AII withdrawal, blood pressure in SHR had fallen from a control value of 172 +/- 3.3 to 146 +/- 3.9 mmHg (p less than 0.01), whereas pressure in WKY had fallen from 116 +/- 3.0 to 107 +/- 4.2 mmHg (statistically non significant). Thus, pressure at 5 h after AII withdrawal was still substantially higher (p less than 0.01) in the SHR than in the WKY. The results demonstrate that the fall in blood pressure following withdrawal of a prolonged infusion of AII in SHR is much less than that reported to occur following withdrawal of a prolonged infusion of vasopressin (AVP) in SHR.     

A possible explanation of genetic hypertension in the spontaneously hypertensive rat

Converting enzyme inhibitors prevent the development of hypertension and normalize arterial blood pressure in spontaneously hypertensive rats (SHR), suggesting a critical role for angiotensin II in genetic hypertension. We hypothesized that the SHR is hyperresponsive to the slow-pressor effect of angiotensin II. To test this hypothesis, 14 SHR and 14 normotensive Wistar Kyoto rats (WKY) were treated chronically with captopril (100 mg X kg-1 X day-1 in drinking water) beginning at 5 weeks of age. At 9 weeks of age, either angiotensin II (125 ng/min; 7 SHR and 7 WKY) or vehicle (7 SHR and 7 WKY) was infused for 2 weeks via an osmotic minipump implanted into the peritoneal cavity. Captopril treatment was maintained and systolic blood pressure was monitored 3 times weekly. Although systolic blood pressure was similar in SHR and WKY infused with vehicle (101 +/- 2 versus 103 +/- 5 mmHg, respectively during the second week), systolic blood pressure in SHR treated with angiotensin II was much greater than systolic blood pressure in WKY treated with angiotensin II (193 +/- 9 versus 132 +/- 11 mmHg, respectively during the second week, p less than 0.001). These results indicate that compared to WKY, SHR are remarkably more sensitive to the slow-pressor effect of chronic, low-dose infusions of angiotensin II. Our results support the hypothesis that the critical genetic defect in SHR is a change in the sensitivity to the slow-pressor effect of angiotensin II.     

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.     

Effect of blood pressure on L-NAME-sensitive component of vasorelaxation in adult rats

The aim of this study was to investigate nitric oxide (NO) production and L-NAME-sensitive component of endothelium-dependent vasorelaxation in adult normotensive Wistar-Kyoto rats (WKY), borderline hypertensive rats (BHR) and spontaneously hypertensive rats (SHR). Blood pressure (BP) of WKY, BHR and SHR (determined by tail-cuff) was 111+/-3, 140+/-4 and 184+/-6 mm Hg, respectively. NO synthase activity (determined by conversion of [(3)H]-L-arginine) was significantly higher in the aorta of BHR and SHR vs. WKY and in the left ventricle of SHR vs. both BHR and WKY. L-NAME-sensitive component of endothelium-dependent relaxation was investigated in the preconstricted femoral arteries using the wire myograph during isometric conditions as a difference between acetylcholine-induced relaxation before and after acute N(G)-nitro-L-arginine methyl ester pre-treatment (L-NAME, 10(-5) mol/l). Acetylcholine-induced vasorelaxation of SHR was significantly greater than that in WKY. L-NAME-sensitive component of vasorelaxation in WKY, BHR and SHR was 20+/-3 %, 29+/-4 % (p<0.05 vs. WKY) and 37+/-3 % (p<0.05 vs. BHR), respectively. There was a significant positive correlation between BP and L-NAME-sensitive component of relaxation of the femoral artery. In conclusion, results suggest the absence of endothelial dysfunction in the femoral artery of adult borderline and spontaneously hypertensive rats and gradual elevation of L-NAME-sensitive component of vasorelaxation with increasing blood pressure.     

High flaxseed (linseed) diet restores endothelial function in the mesenteric arterial bed of spontaneously hypertensive rats.

The effect of high flaxseed diet (HFD) on blood pressure (BP) and mesenteric arterial bed (MAB) reactivity was studied in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. HFD did not affect BP in either SHR (control, 157 +/- 3; HFD, 153 +/- 3 mmHg) or WKY (control, 114 +/- 2; HFD, 117 +/- 2 mmHg) rats. Increases in perfusion pressure of the endothelium-intact MAB to phenylephrine and norepinephrine were higher (p < 0.05) in SHR than in WKY rats and the HFD failed to alter these responses. Vasorelaxant responses to acetylcholine (ACh) and bradykinin (BK) were greater (p < 0.05) in SHR maintained on HFD compared to SHR on control diet. While HFD also enhanced ACh responses in WKY, the effect was less than in SHR. Responses to sodium nitroprusside (SNP), were similar in all groups. Since ACh and BK-induced responses of the MAB were augmented in SHR on HFD, with no changes in BP, it is suggested that HFD improves endothelial vasorelaxant function through a pressure-independent mechanism.     

原发性高血压患者红细胞抗高血压因子对高血压...

The effects of antihypertensive factor (AHF) from erythrocytes of essential hypertensive human subjects on the systolic blood pressure (SBP) and diastolic blood pressure (DBP) in spontaneously hypertensive rats (SHR), renal hypertensive rats (RHR), Wistar-Kyoto rats (WKY) and Wistar rats were examined. Single intraperitoneal injection of AHF (1.6 mg/kg body weight) resulted in a significant decrease in SBP of SHR and RHR. At 10 min postinjection, AHF lowered the SBP in SHR by 34.0 mmHg. SBP recovered to the original level at 3 h. The maximal decrease of SBP in RHR by 92.5 mmHg was at 24h postadministration and the SBP did not recover until the 9th day. When AHF was administered via femoral vein (0.8 mg/kg body weight), the maximal decrease values of the SBP and the DBP were 42.8 and 48.2 mmHg in SHR at 12 min and 38.3 and 42.5 mmHg in RHR at 25 min postinjection respectively. The DBP in Wistar rats decreased considerably (from 96.7 +/- 12.9 to 83.3 +/- 11.7 mmHg) at 5 min postadministration of AHF, but no effect on DBP in WKY rats was observed. The depressor effect of AHF on SBP in RHR was dose-dependent. AHF could also antagonize the pressor effect of norepinephrine in Wistar rats.     

Central cardiovascular effects of baclofen in spontaneously hypertensive rats

This study was conducted to investigate the effects of centrally administered baclofen on blood pressure and heart rate in conscious spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Administration of baclofen (1.0 microgram/kg) into the lateral cerebral ventricle (icv) produced an increase in mean arterial pressure (MAP) in both SHR and WKY rats. The increase in MAP was significantly lower in SHR (13 +/- 3 mmHg) when compared with WKY (27 +/- 5 mmHg). The changes in heart rate (HR) were variable, from no change to a very small increase and did not differ significantly between SHR and WKY rats. The ability of baclofen to interfere with baroreceptor reflexes was also tested in separate experiments. In SHR, icv injection of baclofen (1.0 microgram/kg) significantly suppressed the pressor response and bradycardia evoked by phenylephrine 3.0 micrograms/kg iv, whereas in WKY, the pressor and HR responses to similar injections of phenylephrine were not affected by icv baclofen. Similarly, baclofen treatment modified hypotensive response and reflex tachycardia induced by nitroprusside (10.0 micrograms/kg) iv in SHR but not in WKY rats. Administration of sympathetic ganglionic blocker hexamethonium (HEX; 25 mg/kg) iv produced an equivalent decrease in MAP between SHR and WKY following icv injection of baclofen (1.0 microgram/kg). These results suggest that the effects of baclofen on the baroreceptor reflexes in SHR may not be mediated by a change in peripheral sympathetic tone.     

Effect of 14,15-epoxyeicosatrienoic acid infusion on blood pressure in normal and hypertensive rats

Intravenous (IV) and intraarterial (IA) infusion of 14,15-epoxyeicosatrienoic acid (14,15-EET) produced a dose-dependent decrease in mean arterial blood pressure (MAP) in normal and spontaneously hypertensive rats (SHR). The hypotensive effect of 14,15-EET was observed from 1 microgram/kg to 10 micrograms/kg with a maximum reduction in MAP as much as 45 +/- 6 mmHg in both normal and SHR. In normal rats the hypotensive effect was found to be more pronounced when 14,15-EET was infused IA than IV. This suggests that 14,15-EET may be metabolized as it passes through the lungs. However, in SHR there was no difference in MAP when 14,15-EET was infused either IA or IV. This indicates that there is a differential removal of the epoxide across the pulmonary circulation. Administration of indomethacin failed to inhibit the hypotensive action of 14,15-EET, suggesting that it may not be a cyclo-oxygenase dependent mechanism. However, the PAF antagonist of BN-52021 inhibited the hypotensive action of 14,15-EET. This therefore, suggests that the release of PAF may be involved in the hypotensive action of this epoxide of arachidonic acid.     

Changes in the content of atrial natriuretic factor with the progression of hypertension in spontaneously hypertensive rats

In order to assess possible roles of atrial natriuretic factor (ANF) in spontaneously hypertensive rats (SHR), we examined the content of immunoreactive-ANF in plasma, the atria, hypothalamus and pons of SHR and Wister Kyoto (WKY) rats by radioimmunoassay at different stages of age. With the progression of hypertension, plasma concentration of ANF increased whereas it decreased in the atria in SHR. This suggests ANF is secreted in response to hypertension. On the other hand, at hypothalamus and pons, ANF content was significantly higher in SHR than in WKY rats. This finding suggests possible involvement of ANF in the central regulation of blood pressure.     

A new inorganic vasodilator, trans-[Ru(NO)(NH(3))(4)(POEt)(3)](PF(6))(3): hypotensive effect of endothelium-dependent and -independent vasodilators in different hypertensive animals models.

The hypotensive effect of RuNO was investigated in acute and chronic hypertensive rats, as well as in normotensive rats. Acute hypertension rats were used with 30% increase on basal BP (phenylephrine, angiotensin II (Ang II), N(G)-nitro-L-arginine methyl ester (L-NAME), and adult spontaneously hypertensive rats (SHR) (basal BP 168 +/- 3 mm Hg) were used as models for chronic hypertension. Rats were implanted with catheters (iv/ia) for BP measurements and for in bolus administration of RuNO, sodium nitroprusside (SNP), and acetylcholine (Ach) (10, 20, 40 nmol/kg, iv). The principal findings of this study were: (i) The hypotensive response to RuNO was 150% higher in acutely (phenylephrine and Ang II) and chronically (SHR) hypertensive rats than in normotensive rats, except in the case of L-NAME-induced hypertension (deltaMAP = 10 +/- 1.4 mm Hg). Chronic SHR showed 60% increase (deltaMAP = 19 +/- 0.8 mm Hg) in the effect compared to normotensive rats. (ii) The hypotensive response to SNP was lower (60%) in hypertensive rats than in normotensive rats, when compared to RuNO. However, the responses were similar in L-NAME-induced hypertension (deltaMAP = 30 +/- 2 mm Hg). (iii) The vasodilator response to Ach was increased in rats with Ang II-induced hypertension (deltaMAP = 53 +/- 1 mm Hg) and in SHR (deltaMAP = 67 +/- 3 mm Hg). RuNO response was more potent than SNP in hypertensive models and the increment in relation to normotensive was observed in the phenylephrine- and L-NAME-treated rats. This response could be correlated to the different endothelial dysfunction present in each model.     

The effects of 19-nor-aldosterone on blood pressure of adrenalectomized spontaneously hypertensive rats

The relative hypertensinogenic potencies of recently synthesized 19-nor-aldosterone and its precursor 19-OH-aldosterone were assessed in comparison to that of aldosterone (Aldo) in young (6-week-old) adrenalectomized (ADX) spontaneously hypertensive rats (SHR). Infusion of 19-nor-aldosterone for 2 weeks by Alza mini-osmotic pumps caused significant, dose-dependent increases in the systolic blood pressure (BP) of young ADX SHR; dosages of 0.1 and 0.5 microgram/day raised the BP from 127 +/- 2 mmHg to 164 +/- 9 and 180 +/- 11 mmHg, respectively. During this period, control ADX SHR receiving vehicle only remained normotensive. Similar increases in BP were seen only with infusion of slightly higher dosages of Aldo (0.5 and 1.0 micrograms/day). In contrast, 19-OH-aldosterone infused at higher dosages (10 or 25 micrograms/day) caused little change in BP of ADX SHR. Full suppression of plasma renin activity (PRA) was observed with 0.1 and 0.5 microgram/day 19-nor-aldosterone, whereas Aldo caused similar decreases in PRA only at dosages of 0.5 microgram/day and higher. Interestingly, although infusions of 19-OH-aldosterone did not cause a significant change in BP, these dosages (10 and 25 micrograms/day) significantly suppressed PRA. These studies which show that 19-nor-aldosterone is equipotent to Aldo, and perhaps slightly more active in ADX SHR, indicate that 19-nor-aldosterone is a potentially important hypertensinogenic steroid.     

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.     

Nonshivering thermogenesis and brown fat in spontaneously hypertensive rats

Oxygen consumption was measured before and during infusion of the catecholamine isoproterenol in age-matched spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats. Mass-independent rates of oxygen consumption of anesthetized 7-week-old rats were similar in the WKY and SHR rats (11.08 +/- 0.74 and 11.33 +/- 0.82 ml O2 min-1 kg-.67, respectively). Catecholamine infusion elicited increased total oxygen consumption in both WKY and SHR animals (15.0 +/- 1.0 and 14.9 +/- 1.2 ml O2 min-1 kg-.67, respectively), and the magnitude of these increases did not significantly differ. To assess whether there were changes in the metabolic state of brown adipose tissue, the major site of catecholamine-induced thermogenesis in rats, enzymes whose activity is proportional to aerobic capacity were assayed in vitro. In both the interscapular and cervical brown fat depots, maximal citrate synthase and maximal HOAD (beta-hydroxyacyl-CoA dehydrogenase) activities were similar in SHR and WKY rats. There were also no significant differences in brown fat protein content, suggesting no differential growth of this tissue in the two rat strains. Our results indicate that the nonshivering thermogenic capacity of the hypertensive SHR rats does not differ from that of the normotensive WKY animals.     

Effects of chronic treatment with a novel angiotensin converting enzyme inhibitor, CS622, and a vasodilator, hydralazine, on atrial natriuretic factor (ANF) in spontaneously hypertensive rats (SHR)

We studied the effects of chronic treatment with a novel angiotensin converting enzyme inhibitor, alpha-[(2S,6R)-6-[(1S)-1-ethoxycarbonyl-3-phenylpropyl]amino-5-oxo-2- (2-thienyl)perhydro-1,4-thiazepin-4-yl]acetic acid.HCl (CS622), and a vasodilator, hydralazine, on plasma atrial natriuretic factor (ANF) levels and kidney ANF receptors in spontaneously hypertensive rats (SHR). Plasma ANF level was decreased and cardiac hypertrophy reduced in CS622 treated SHR, but not in hydralazine treated SHR, although blood pressure was lowered similarly in both SHR groups. The binding capacity of kidney ANF receptors increased and the affinity decreased in CS622 treated SHR compared to untreated SHR. These results suggest that decrease of plasma ANF results from decreased cardiac load but not from lowered blood pressure, and that changes in ANF receptors result from increased plasma ANF.