ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The susceptibility of immature and adult animals to various environmental factors often differs because the response of the young organism can only involve those regulatory mechanisms that are available at the particular stage of development. Increased sensitivity to certain (e.g., hypertensive) stimuli may be limited to a relatively short age period that is usually characterized by the maturation of some, important physiological functions. High salt intake seems to influence the animals especially during the weaning period and prepuberty, in the course of which profound developmental changes of circulation, electrolyte metabolism, and neurohumoral regulation have been demonstrated. Indeed, salt-dependent forms of experimental hypertension are more severe when they are induced in immature animals. Moreover, substantial differences in hemodynamics, distribution of body fluids, and involvement of pressor and natriuretic agents indicate that the mechanisms of salt hypertension need not be the same in immature and adult animals. For this reason, increased attention should be paid to developmental factors in the study of induced forms of experimental hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

A potent renin inhibitor, U-71038 (BK-Pro-Phe-JV-MeHis-Leuψ[CHOHCH2]Val-Ile-Amp), was tested for oral effectiveness. Enzyme kinetic studies indicated that U-71038 was a competitive inhibitor of hog renin with an inhibitor constant (K1) value of 12 nM. Intravenous as well as oral administration of U-71038 to anesthetized, ganglion-blocked rats infused with hog renin elicited doserelated hypotensive responses. Intravenous administration of U-71038 to conscious, sodium-depleted monkeys caused dose-related decreases of blood pressure and plasma renin activity without affecting heart rate. Similarly, the oral administration of U-71038 at 50 mg/kg to conscious, sodium-depleted monkeys elicited a pronounced hypotension and decrease in plasma renin activity that persisted for 5 hours. The hypotensive responses elicited by intravenous and oral administration of U-71038 to hog renin-infused rats and sodium-depleted monkeys were shown to be due entirely to inhibition of the renin-angiotensin system. A comparison of the results obtained after the intravenous administration of U-71038 with the results obtained after the oral administration of U-71038 implied that at least 10% of the orally administered U-71038 must have been absorbed to cause the observed effects in hog renin-infused rats and sodium-depleted monkeys. The studies demonstrated that an inhibitor of renin with a long duration of action and with oral effectiveness is a feasible entity.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The present study examines effects of administration of OKY 046, an inhibitor of thromboxane synthesis, for 100 days on systemic blood pressure and renal function in spontaneously hypertensive rats and in normotensive control rats. Untreated spontaneously hypertensive rats had higher values for thromboxane excretion in the urine and higher values for blood pressure than did normotensive control rats. Administration of OKY 046 decreased systolic and mean arterial blood pressure and urinary excretion of thromboxane and protein in spontaneously hypertensive rats. Administration of OKY 046 decreased thromboxane excretion in the urine of normotensive control rats but had no effect on blood pressure or protein excretion. Renal function, as assessed by the clearances of inulin and p-aminohippuric acid, was greater in spontaneously hypertensive rats treated with OKY 046 than in those receiving vehicle alone. In normotensive control rats, OKY 046 administration did not affect renal function. These results suggest that increased renal synthesis of thromboxane may play a role in the pathogenesis of the elevated blood pressure of spontaneously hypertensive rats.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

In the rat, angiotensin II receptors of the adrenal glomerulosa and smooth muscle undergo reciprocal regulatory changes that parallel the changes in target cell sensitivity to angiotensin II during altered sodium intake. In primates, the relative importance of angiotensin II receptor regulation during sodium-induced changes in angiotensin II sensitivity is not clear. To evaluate the role of angiotensin II receptor regulation in the primate, we analyzed the changes in angiotensin II receptors of adrenal and bladder membrane-rich particles after 4 to 6 days of high or low sodium intake in the monkey (Macaca fascicularis). Consistent with the decreased pressor response to angiotensin II, smooth muscle angiotensin II receptors were fewer in sodium-restricted monkeys (93 ± 17 fmol/mg) than in sodium-loaded monkeys (171 ± 6 fmol/mg). However, in contrast to the rat. changes in zona glomerulosa angiotensin II receptors in monkey adrenal were similar to those in smooth muscle, decreasing with sodium restriction and increasing with sodium loading (344 ± 64 and 660 ± 68 fmol/mg, respectively). There was no change in angiotensin II receptor affinity in either smooth muscle or adrenal particles during altered sodium intake. Concomitant with the decrease in adrenal angiotensin II receptors, 18-hydroxylase activity was increased twofold in adrenal mitochondria from sodium-restricted monkeys (74 ± 8 fmol/mg/min) compared with sodium-loaded animals (28 ±11 fmol/mg/min). The increased sensitivity of the primate adrenal to angiotensin II despite a fall in angiotensin II receptors indicates that full activation of steroidogenesis by angiotensin II can be maintained with partial receptor occupancy. These results suggest that postreceptor events including increased 18-hydroxylase activity are important determinants of the aldosterone response to angiotensin II during sodium restriction in primates.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Neural and angiotensin-mediated influences that alter hemodynamic and excretory behavior of the nonclipped kidney of two-kidney, one clip hypertensive rats were assessed by sequential acute surgical denervation of the nonclipped kidney and intravenous infusion of converting enzyme inhibitor (SQ 20881), 3 mg/kg hr. Normal and two-kidney, one clip hypertensive rats (0.2-mm silver clip on the right renal artery 3–4 weeks before study) were prepared to allow study of each kidney. Mean arterial blood pressure of two-kidney, one clip hypertensive rats fell significantly from control values of 149 ± 6 to 135 ± 6 mm Hg after denervation of the nonclipped kidney. Despite this decrease in arterial pressure, the nonclipped kidney exhibited significant increases in glomerular filtration rate (from 1.00 ± 0.08 to 1.24 ± 0.08 ml/min), sodium excretion (from 88 ± 39 to 777 ± 207 nEq/min), fractional sodium excretion (from 0.06 ± 0.02 to 0.54 ± 0.14%), and urine flow rate (from 3.7 ± 0.5 to 8.2 ±1.1 fiVmin). A significant decrease in glomerular filtration rate (from 1.12 ± 0.07 to 0.85 ± 0.08 ml/min) with no change in excretory function was observed for the clipped kidney following denervation of the nonclipped kidney. Intravenous addition of converting enzyme inhibitor significantly increased renal blood flow (from 7.0 ± 1.3 to 10.6 ± 1.5 ml/min) and sodium excretion (from 777 ± 207 to 1384 ± 425 nEq/min) for the nonclipped kidney; blood pressure decreased from 135 ± 6 to 123 ± 4 mm Hg, and renal vascular resistance decreased significantly (from 22 ± 3 to 13 ± 2 mm Hg -min/ml). In normal rats acute surgical denervation of one kidney resulted in reductions in arterial pressure and ipsilateral increases in urine flow rate and sodium and potassium excretion that were of smaller magnitude than those observed in the denervated kidney of the two-kidney, one clip hypertensive rats; sodium excretion decreased slightly in the untouched, innervated kidney. Addition of converting enzyme inhibitor produced a further increase of sodium excretion hi both kidneys. Renal hemodynamics were not altered in either kidney throughout the experiment. These results suggest that renal neural influences, in addition to angiotensin-mediated effects, contribute to the altered hemodynamic and excretory behavior of the nonclipped kidney of the two-kidney, one clip hypertensive rat.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The effect of antihypertensive drug treatment on aortic DNA synthesis was examined in rats with two-kidney, one clip renal hypertension and in spontaneously hypertensive rats (SHR). In two-kidney, one clip hypertensive rats, hypertension developed over a 2-week period. Four days after clipping the renal artery, during the onset of hypertension, there was an increase in aortic DNA synthesis. Aortic DNA synthesis was also increased 3 weeks later, when hypertension had been established. Captopril, hydralazine, and verapamil were each able to prevent the increase in aortic DNA synthesis and the rise in blood pressure when given throughout the first 5 days of the developing phase of hypertension, or when given to rats with established hypertension. Drug treatment of shamoperated rats had no significant effect on DNA synthesis, although blood pressure was decreased. There were no differences in blood pressure or aortic DNA synthesis in 4-week-old SHR, as compared with age-matched Wistar-Kyoto (WKY) controls or normal Wistar rats. At 17 weeks of age, when hypertension was established, aortic DNA synthesis was significantly enhanced in the SHR. Captopril or hydralazine treatment was able to reduce blood pressure and DNA synthesis to levels seen in the WKY. At 21 weeks of age, DNA synthesis in the SHR had declined to the same levels as in the WKY. Captopril, hydralazine, and verapamil may have a common ability to reduce intracellular calcium and therefore inhibit DNA synthesis. In support of this, ouabain treatment, which increases intracellular calcium by inhibiting the Na+-K+pump, produced a significant increase in the rate of DNA synthesis. These findings suggest that the increase in aortic DNA synthesis may be dissociated from the development of hypertension and that antihypertensive drug treatment can inhibit the increase in DNA synthesis even in animals with established hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The changes in ventricular isomyosin composition and Ca2+-activated ATPase activity occurring with regression of both hypertension and cardiac hypertrophy were investigated by using polyacrylamide gel electrophoresis under nondenaturing conditions, heavy chain peptide mapping, and an enzymatic assay. Eight control male Wistar rats and 14 two-kidney, one clip (Goldblatt II) hypertensive rats were studied from the fifth week of age. At 10 weeks of age, five Goldblatt II rats and four normotensive controls were killed. Five other Goldblatt II rats underwent nephrectomy of the ischemic kidney, which resulted in subsequent normalization of blood pressure. The remaining four control, four Goldblatt II rats, and five nephrectomized rats were killed at 15 weeks of age. Both the 10-and 15-week-old hypertensive rats had a significantly higher (p< 0.001) biventricular weight to body weight ratio than the age-matched controls (3.84 ± 0.76 × 10−2vs 2.75 ± 0.25 × 10−2; 5.93 ± 2.26 × 10–2 vs 2.65 ± 0.17 × 10−2). The 15-week-old nephrectomized rats had a biventricular weight to body weight ratio (2.90 ± 0.25 × 10−2) close to that of age-matched controls and significantly lower (p< 0.05) than that of age-matched hypertensive rats. In both the 10-and 15-week-old hypertensive rats left ventricular myosin Ca2+-activated ATPase activity was significantly lower (p< 0.001) than in the age-matched controls (0.44 ± 0.03 vs 0.59 ± 0.06; 0.24 ± 0.05 vs 0.48 ± 0.05). Conversely, in nephrectomized rats activity was similar to that of age-matched controls (0.46 ± 0.04) and significantly higher (p< 0.001) than that of age-matched hypertensive rats. The expression of “slow” isoenzymes of myosin V2and V1was evident in the hypertensive animals, which displayed a decrease of the “fast” V] isoenzyme. Through peptide mapping of myosin heavy chains, an additional band was found in both groups of hypertensive animals that was absent in the age-matched controls. Nephrectomized 15-week-old rats showed a ventricular isomyosin composition and peptide mapping similar to that of age-matched controls. In conclusion, with normalization of blood pressure, complete reversal of cardiac hypertrophy was achieved and the biochemical and molecular properties of left ventricular myosin were fully restored.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

We previously showed that adrenal renin is highest in the rat zona glomerulosa (ZG) and that low sodium or high potassium and nephrectomy increase adrenal ZG renin and aldosterone. Dahl salt-sensitive rats (S) have been shown to have lower plasma renin activity and plasma aldosterone and higher plasma 18-hydroxy-ll-deoxycorticosterone than Dahl salt-resistant rats (R). In this study we assess the possible role of adrenal ZG renin in the suppression of aldosterone in S rats. Adrenal ZG renin was significantly decreased in S as compared with R rats even at 6 weeks of age, when both S and R rats are still normotensive (S = 7.2 ± 0.2, R = 18.0 ± 1.6 ng angiotensin I/mg protein/hr). Adrenal ZG aldosterone was also significantly lower in S than in R rats (S = 21.1 ± 4.3, R = 39.5 ± 3.6 ng/mg protein). Furthermore, the rise in adrenal ZG renin and aldosterone after nephrectomy in S rats was significantly less than that in R rats. To determine if the suppressed adrenal ZG renin of S rats is due to volume expansion, we studied the effect of a sodium-deficient diet on adrenal ZG renin in S and R rats. After 2 weeks of a sodium-deficient diet S rats had significantly lower basal adrenal ZG renin than did R rats (S = 7.6 ± 0.4, R = 21.7 ± 1.9 ng angiotensin I/mg protein/hr) and a marked blunting of the adrenal ZG renin response to nephrectomy (S = 13.6 ± 1.1, DR = 167 ± 16.1 ng angiotensin I/mg protein/hr). Our previous report of blunting of the nephrectomy response by indomethacin suggests a role for prostaglandins in the regulation of adrenal renin. Adrenal ZG prostaglandin E2in S rats was also significantly lower than in R rats (S = 0.22 ± 4.3, R = 0.40 ± 0.05 ng/mg protein). These data indicate that the low adrenal ZG renin in S rats is associated with low plasma aldosterone and that the low adrenal ZG renin level of S rats is not due to volume expansion and probably represents a genetic abnormality of the salt-sensitive strain or the low adrenal ZG prostaglandin E2level, or both.

ISSN:0194-911X    

出版商:OVID    

年代:1986

数据来源: OVID