Parathyroid Hormone- and Deoxycorticosterone Acetate-Induced Hypertension in the Rat

1980 ◽  
Vol 58 (5) ◽  
pp. 365-371 ◽  
Author(s):  
A. Berthelot ◽  
A. Gairard

1. Hypertension induced by treatment with deoxycorticosterone acetate and sodium chloride was studied in male Sprague-Dawley rats and related to parathyroid hormone secretion. 2. Lack of parathyroid hormone (due to parathyroidectomy) or decreased parathormone secretion (due to a high-calcium diet) partially inhibited the development of arterial hypertension. 3. In contrast, in thyroparathyroidectomized rats supplemented with thyroxine, the administration of parathyroid hormone rapidly elevated arterial blood pressure. 4. Maintaining a physiological concentration of serum calcium in the absence of parathyroid hormone (by feeding a high-calcium diet to parathyroidectomized rats) was not sufficient to establish mineralocorticoid hypertension. 5. These results show that parathyroid hormone is necessary for the complete development of mineralocorticoid hypertension.

1991 ◽  
Vol 260 (4) ◽  
pp. E608-E612
Author(s):  
M. Michalkiewicz ◽  
J. M. Connors ◽  
L. J. Huffman ◽  
Z. Pietrzyk ◽  
G. A. Hedge

It has been shown that the compensatory growth of the thyroid gland and the compensatory increase in hormone secretion that occur after hemithyroidectomy are preceded by a dramatic increase in thyroid blood flow (BF). These alterations in the thyroid remnant may be due to the concomitant increase in plasma thyrotropin (TSH) concentrations. It has been suggested, however, that the compensatory thyroid growth may also involve a neural reflex. In this study we have investigated the role of TSH in mediating the compensatory alterations in thyroid BF and mass after subtotal thyroidectomy. Male Sprague-Dawley rats were anesthetized with ether for surgical or sham hemithyroidectomy. One-half of the hemithyroidectomized rats (HTX) received no further treatment; in the other one-half of the HTX rats (Clamp), plasma TSH levels were maintained at levels comparable with those in sham-operated animals by initiating constant thyroid hormone replacement beginning at the time of hemithyroidectomy. Plasma samples for TSH, 3,5,3'-triiodothyronine, and thyroxine radioimmunoassays were obtained 2, 7, 14, and 21 days after surgery. Thyroid BF was determined at 1, 2, and 3 wk after surgery by the reference sample version of the radioactive microsphere technique (141Ce, 15 microns diameter). Plasma TSH levels and thyroid lobe weight were significantly elevated in HTX rats but not in Clamp rats. Thyroid BF was markedly increased in HTX rats. Thyroid BF was also significantly increased in Clamp rats despite the suppression of the rise in plasma TSH concentration, but this increase was less than that in HTX rats. Neither hemithyroidectomy nor Clamp treatments had any effect on arterial blood pressure or BF to other tissues (e.g., kidney).(ABSTRACT TRUNCATED AT 250 WORDS)


2003 ◽  
Vol 285 (5) ◽  
pp. H1882-H1889 ◽  
Author(s):  
Pasi Jolma ◽  
Peeter Kööbi ◽  
Jarkko Kalliovalkama ◽  
Mika Kähönen ◽  
Meng Fan ◽  
...  

Chronic renal failure (CRF) is associated with abnormal lipid metabolism and high prevalence of vascular complications. Calcium salts are commonly used in CRF as phosphate binders. Increased calcium intake may also lower plasma cholesterol and beneficially influence vascular tone. Therefore, we investigated the influence of increasing dietary calcium from 0.3% to 3.0% for 8 wk after 5/6 nephrectomy (NTX) on plasma cholesterol and mesenteric resistance vessel tone in male Sprague-Dawley rats. The groups were Sham, Sham-Calcium, NTX, and NTX-Calcium ( n = 10–11). Blood pressure was modestly elevated after NTX, whereas the plasma creatinine, urea nitrogen, phosphate, and parathyroid hormone levels were clearly increased. The high-calcium diet suppressed plasma phosphate and parathyroid hormone but was without effect on blood pressure. The NTX resulted in 1.6-fold elevation in plasma total cholesterol and 40% reduction in high density-to-low density lipoprotein ratio (HDL/LDL). However, the lipid profile in NTX rats on the high-calcium diet did not differ from sham-operated controls. The endothelium-mediated relaxations induced by acetylcholine were impaired in NTX rats, whereas the response was normalized by a high-calcium diet. No differences in vasorelaxations by the endothelium-independent vasodilator nitroprusside were detected. In conclusion, improved vasorelaxation after a high-calcium diet could be due to reduced plasma total cholesterol and ameliorated HDL/LDL ratio, although decreased plasma phosphate and parathyroid hormone may also play a significant role in the vascular effects of increased calcium intake.


1979 ◽  
Vol 57 (2) ◽  
pp. 157-162 ◽  
Author(s):  
A. Berthelot ◽  
R. Schleiffer ◽  
A. Gairard

We studied the importance of parathyroids in the development of mineralocorticoid hypertension in male Sprague–Dawley rats. Ablation of the parathyroids 1 week before deoxycorticosterone acetate (DOCA) + NaCl administration prevented development of hypertension (for 1 year). But ablation of parathyroids 2 weeks after the start of treatment has no effect on the development of arterial hypertension. Autotransplantation of parathyroids in thyroidectomized rats caused a recurrence of mineralocorticoid hypertension, which was completed after DL-thyroxine supplementation: blood pressure levels were nearly the same as in DOCA sham rats. We conclude that parathyroid glands favor the establishment of mineralocorticoid hypertension in the rat. These results raise the question of the mechanism of action of parathyroid hormone in the hypertensive process.


2008 ◽  
Vol 295 (5) ◽  
pp. R1546-R1554 ◽  
Author(s):  
Melissa Li ◽  
Xiaoling Dai ◽  
Stephanie Watts ◽  
David Kreulen ◽  
Gregory Fink

Endothelin (ET) type B receptors (ETBR) are expressed in multiple tissues and perform different functions depending on their location. ETBR mediate endothelium-dependent vasodilation, clearance of circulating ET, and diuretic effects; all of these should produce a fall in arterial blood pressure. However, we recently showed that chronic activation of ETBR in rats with the selective agonist sarafotoxin 6c (S6c) causes sustained hypertension. We have proposed that one mechanism of this effect is constriction of capacitance vessels. The current study was performed to determine whether S6c hypertension is caused by increased generation of reactive oxygen species (ROS) and/or activation of the sympathetic nervous system. The model used was continuous 5-day infusion of S6c into male Sprague-Dawley rats. No changes in superoxide anion levels in arteries and veins were found in hypertensive S6c-treated rats. However, superoxide levels were increased in sympathetic ganglia from S6c-treated rats. In addition, superoxide levels in ganglia increased progressively the longer the animals received S6c. Treatment with the antioxidant tempol impaired S6c-induced hypertension and decreased superoxide levels in ganglia. Acute ganglion blockade lowered blood pressure more in S6c-treated rats than in vehicle-treated rats. Although plasma norepinephrine levels were not increased in S6c hypertension, surgical ablation of the celiac ganglion plexus, which provides most of the sympathetic innervation to the splanchnic organs, significantly attenuated hypertension development. The results suggest that S6c-induced hypertension is partially mediated by sympathoexcitation to the splanchnic organs driven by increased oxidative stress in prevertebral sympathetic ganglia.


1988 ◽  
Vol 254 (1) ◽  
pp. E63-E70 ◽  
Author(s):  
J. J. Morrissey

The influence of phorbol myristate acetate (PMA), an activator of protein kinase c, on the secretion of parathyroid hormone from collagenase-dispersed bovine parathyroid cells was tested. The cells were incubated at low (0.5 mM) or high (2.0 mM) concentrations of calcium in the medium, and the hormone secreted into the medium was measured by a radioimmunoassay that recognizes both intact and C-terminal fragments of hormone. At low calcium, the secretory rate averaged 32 +/- 3.8 ng.h-1.(10(5) cells)-1. The addition of 1.6 microM PMA did not affect secretion. At high calcium there was a significant suppression of secretion by 38% to 19.8 +/- 3 ng.h-1.(10(5) cells)-1. The addition of 1.6 microM PMA significantly stimulated hormone secretion to 35.8 +/- 8 ng.h-1.(10(5) cells)-1, a rate indistinguishable from low calcium. This stimulatory effect of PMA at high calcium was seen at PMA concentrations as low as 1.6 nM, did not occur with a biologically inactive 4 alpha-isomer of phorbol ester, and was independent of changes in cellular adenosine 3',5'-cyclic monophosphate levels. Examination of 32P-labeled phosphoproteins by two-dimensional gel electrophoresis revealed acidic proteins of approximately 20,000 and 100,000 Da that were phosphorylated at low and high calcium + 1.6 microM PMA but not at high calcium alone. The protein kinase c activity associated with the membrane fraction of parathyroid cells significantly decreased 40% when the cells were incubated at high vs. low calcium. The data suggest that calcium may regulate parathyroid hormone secretion through changes in protein kinase c activity of the membrane fraction of the cell and protein phosphorylation.


Author(s):  
Alyssa K. Phillips‐Eakley ◽  
Mikaela L. McKenney‐Drake ◽  
Martin Bahls ◽  
Sean C. Newcomer ◽  
John S. Radcliffe ◽  
...  

1985 ◽  
Vol 59 (5) ◽  
pp. 1410-1415 ◽  
Author(s):  
K. D. Marcus ◽  
C. M. Tipton

The influence of endurance training on functional capacity [maximal O2 consumption (VO2 max)], caudal arterial blood pressure, and myocardial capillary density were investigated in normotensive rats and rats made hypertensive using the two-kidney one-clip approach (Goldblatt's hypertension). Male Sprague-Dawley rats were assigned to sham (N: 120–140 mmHg), moderately hypertensive (MH = 0.30-mm clips, 150–170 mmHg), or severely hypertensive (SH = 0.25-mm clips, 190–230 mmHg) groups. Rats designated to be runners (T) were exercised on a motor-driven treadmill equal to 50–70% of their VO2 max values for 8–12 wk. Compared with their nontrained (NT) controls, training was associated with significantly higher VO2 max values (12–15%) and muscle cytochrome-c oxidase activities (33–78%). Resting systolic blood pressure was not significantly changed in the N-and MH-T subgroups; however, it was 20–30 mmHg higher in the SH-T subgroup. Mean absolute heart weight for only the N-T group was significantly heavier than their NT controls. However, the mean predicted heart weights (heart wt = 0.639 X body wt of N-NT + 0.001 g) of the two SH groups were significantly higher than expected. The SH-T group had a lower (11%) subepicardial capillary density mean than its NT control and significantly fewer capillaries in the subendocardial region than the other five subgroups. It was concluded that moderate exercise training appeared to be detrimental to rats with severe hypertension because it increased resting blood pressure and decreased myocardial capillary density, even though it improved their functioning capacity.


1992 ◽  
Vol 2 (11) ◽  
pp. 1601-1607
Author(s):  
J Isaac ◽  
R P Glahn ◽  
M M Appel ◽  
M Onsgard ◽  
T P Dousa ◽  
...  

Dopamine (DA) is natriuretic and phosphaturic. However, whether the effect of DA on Pi reabsorption is a consequence of its effect on sodium transport is not known. Therefore, this study was performed to determine the effect of DA on the maximal transport of phosphate (TmPi), and upon the capacity of renal proximal brush border membrane (BBM) for (Naextra-vesicular greater than Naintravesicular)-gradient-dependent transport of Pi, as compared with the transport of other solutes. Graded infusions of Pi (0, 1, 2, and 3 mumols/min) were given to thyroparathyroidectomized male Sprague-Dawley rats in the presence of vehicle (0.9% NaCl; N = 5), DA 15 micrograms/kg/min; N = 6), or parathyroid hormone ((PTH); 1 U/kg/min; N = 5). The TmPi for rats infused with DA (3.3 +/- 0.3 mumol/mL) was significantly less than the TmPi for saline control rats (4.4 +/- 0.2 mumol/mL). Rats infused with PTH exhibited the lowest TmPi (1.8 +/- 0.3 mumol/mL). No differences in sodium excretion were observed among any of the groups. Na-dependent Pi transport was studied in BBM vesicles (BBMV) prepared from rats fed a low-phosphate diet for 2 days that were anesthetized, acutely thyroparathyroidectomized, and systemically infused with DA (350 micrograms bolus, plus 35 micrograms/kg/min; N = 8), PTH (33 U/kg bolus, followed by a continuous infusion of 1 U/kg/min; N = 6), or vehicle (1 mL/kg bolus, plus 2 mL/h constant infusion of 0.9% NaCl; N = 8) for 90 min. DA significantly inhibited the Na cotransport of Pi by 22.4 +/- 4.1% (P less than 0.01) as compared with the control group.(ABSTRACT TRUNCATED AT 250 WORDS)


2006 ◽  
Vol 291 (1) ◽  
pp. F49-F57 ◽  
Author(s):  
Swasti Tiwari ◽  
Randall K. Packer ◽  
Xinqun Hu ◽  
Yoshihisa Sugimura ◽  
Joseph G. Verbalis ◽  
...  

Previously, we demonstrated that rats undergoing vasopressin escape had increased mean arterial blood pressure (MAP), plasma and urine aldosterone, and increased renal protein abundance of the α-subunit of the epithelial sodium channel (ENaC), the thiazide-sensitive Na-Cl cotransporter (NCC), and the 70-kDa band of γ-ENaC (Song J, Hu X, Khan O, Tian Y, Verbalis JG, and Ecelbarger CA. Am J Physiol Renal Physiol 287: F1076–F1083, 2004; Ecelbarger CA, Knepper MA, and Verbalis JG. J Am Soc Nephrol 12: 207–217, 2001). Here, we determine whether changes in these renal proteins and MAP require elevated aldosterone levels. We performed adrenalectomies (ADX) or sham surgeries on male Sprague-Dawley rats. Corticosterone and aldosterone were replaced to clamp these hormone levels. MAP was monitored by radiotelemetry. Rats were infused with 1-deamino-[8-d-arginine]-vasopressin (dDAVP) via osmotic minipumps (5 ng/h). At day 3 of dDAVP infusion, seven rats in each group were offered a liquid diet [water load (WL)] or continued on a solid diet (SD). Plasma aldosterone and corticosterone and urine aldosterone were increased by WL in sham rats. ADX-WL rats escaped, as assessed by early natriuresis followed by diuresis; however, urine volume and natriuresis were somewhat blunted. WL did not reduce the abundance or activity of 11-β-hydroxsteroid dehydrogenase type 2. Furthermore, the previously observed increase in renal aldosterone-sensitive proteins and escape-associated increased MAP persisted in clamped rats. The densitometry of immunoblots for NCC, α- and γ-70 kDa ENaC, respectively, were (% sham-SD): sham-WL, 159, 278, 233; ADX-SD, 69, 212, 171; ADX-WL, 116, 302, 161. However, clamping corticosteroids blunted the rise at least for NCC and γ-ENaC (70 kDa). Overall, the increase in aldosterone observed in vasopressin escape is not necessary for the increased expression of NCC, α- or γ-ENaC or increased MAP associated with “escape.”


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