Hypotensive properties of antibodies directed against an endogenous pressor peptide isolated from rat blood

1989 ◽  
Vol 67 (12) ◽  
pp. 1580-1585 ◽  
Author(s):  
Daniel G. Todd ◽  
William D. McCumbee ◽  
Gary L. Wright ◽  
William Kopp ◽  
Vernon E. Reichenbecher

Hypertensive factor (HF), a compound isolated from the erythrocytes of rats and tentatively identified as a peptide, has been shown to influence tissue calcium metabolism and induce prolonged blood pressure elevation. In the present study, we investigated the biological properties of antibodies directed against this peptide. Partially purified antibody preparations significantly decreased HF stimulation of lanthanum-resistant calcium uptake in rat aortic tissue in vitro. Infusion of the antibody preparation into spontaneously hypertensive (SH) or normotensive Sprague–Dawley rats resulted in a rapid decline in mean blood pressure of 54 and 34 Torr (1 Torr = 133.332 Pa), respectively. In contrast, infusion of the serum immunoglobulin preparations from controls (unimmunized and ovalbumin-immunized rabbits) had no significant effect on the blood pressure of SH or normotensive rats. The systolic blood pressure of SH rats was reduced for at least 72 h following a single injection of the antibody preparations, whereas the blood pressure of normotensive rats had returned to normal levels within 24 h following antibody injection. The results indicate that the anti-HF antibody preparation antagonizes the stimulation of calcium uptake by the peptide and acutely lowers blood pressure in SH and normotensive rats.Key words: antibodies, blood pressure regulation, hypertensive factor, spontaneously hypertensive rat.

1987 ◽  
Vol 252 (3) ◽  
pp. R554-R561 ◽  
Author(s):  
W. N. Henley ◽  
A. Tucker

The mechanism by which chronic, moderate, hypobaric hypoxia attenuates systemic systolic blood pressure (SBP) in the spontaneously hypertensive rat (SHR) was investigated in a three-part study. In experiment 1, 10 wk of hypoxia (3,658 m altitude) commencing in 7-wk-old rats was partially effective in preventing the rise in SBP [hypoxic SHR (SHR-H) 154 mmHg vs. normoxic SHR (SHR-N) 180 mmHg; P less than 0.01]. When hypoxia was initiated in 5-wk-old SHR (experiments 2 and 3), protection against hypertension was nearly complete (experiment 2: SHR-H 122 mmHg vs. SHR-N 175 mmHg; P less than 0.001; experiment 3: 135 vs. 152 mmHg, respectively; P less than 0.05). Elevations in O2 consumption (VO2) and rectal temperature (Tre) in SHR vs. normotensive [Wistar-Kyoto (WKY)] rats provided evidence that the SHR is a hypermetabolic animal. Thyroid hormonal indices suggested that SHR changed from a low to high thyroid status at a time that rapid blood pressure elevation occurred; however, hypoxia did not influence thyroid status. Acute, significant decrements in VO2 and Tre in SHR-H (experiments 2 and 3) accompanied the attenuation of SBP by hypoxia, whereas large decrements in VO2 and SBP did not occur in hypoxic WKY. Timely administration of moderate hypoxia protects against the development of hypertension in the SHR. This protection may relate to a metabolic adaptation made by the hypoxic SHR.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ko Takesue ◽  
Takuya Kishi ◽  
Yoshitaka Hirooka

Introduction: A recent paradigm shift in cardiovascular pathophysiology is the impact of inflammation on hypertension. Inflammation within the paraventricular nucleus of the hypothalamus (PVN) is an important pathology of sympathetic hyperactivity, and is mainly mediated by innate immune cells, microglia. Activated microglia with alteration of their morphology produce inflammatory cytokines. Previous reports demonstrated that microglia within the PVN have activated morphology in angiotensin II-induced hypertensive rats and spontaneously hypertensive rats compared with normotensive control Sprague-Dawley rats or Wistar-Kyoto (WKY) rats. However, the role of activated microglia in the PVN in blood pressure elevation associated with sympathetic hyperactivity remains unknown. In the present study, we determined whether inhibition of microglial activation within the PVN attenuates the blood pressure elevation in genetically hypertensive rats. Methods and Results: We evaluated the activation of PVN microglia, identified by microglia specific ionized calcium-binding adaptor molecule 1 immunoreactivity, by measuring the roundness and the perimeter of microglia at 6 weeks of age, early hypertension development phase in stroke-prone spontaneously hypertensive rats (SHRSP) and compared with them in age-matched normotensive WKY rats. At 6 weeks of age, increased roundness and shortening of perimeter of microglia, indicating activated microglia, were observed in SHRSP compared with those in WKY rats. Then, we performed intracerebroventricular (ICV) administration of minocycline (5 μg/h) to deactivate microglia at 6 weeks of age for 4 weeks. ICV administration of minocycline significantly attenuated systolic blood pressure elevation in SHRSP over 4 weeks (at the end of experiments; 203.2±2.2 mm Hg vs. 215.9±2.7 mm Hg, n=8-9, P<0.05), but not in WKY rats. At 10 weeks of age, morphological analysis revealed that ICV minocycline significantly decreased the roundness and increased the perimeter of microglia, indicating deactivation of microglia, within the PVN in SHRSP. Conclusions: Hypothalamic activated microglia with morphologic changes accelerate blood pressure elevation during the hypertension development phase in SHRSP.


1986 ◽  
Vol 64 (4) ◽  
pp. 424-429
Author(s):  
G. L. Wright ◽  
G. O. Rankin ◽  
W. D. McCumbee

The present report describes some aspects of the effects of a recently described antihypertensive extract of erythrocytes (AHF) on calcium uptake and efflux in rat aortae. AHF was found to be present in the erythrocytes of both spontaneously hypertensive rats and normotensive rats. Furthermore, AHF obtained from erythrocytes of SH rats was shown to be equally effective in suppressing lanthanum-resistant calcium uptake in aortae from hypertensive and normotensive rats. AHF treatment prior to incubation of aortae with 45Ca caused an apparent increase in the total 45Ca uptake. The analysis of calcium washout curves obtained for tissue in calcium-free or lanthanum-containing media indicated that AHF had no significant effect on the rate of calcium loss from the slow component of efflux, though this compartment tended to be reduced in size. This indicated that the increase in the 45Ca content of AHF-exposed aortae prior to rinsing was confined to the rapid component of efflux. The loss of calcium from the rapidly exchanging compartment was enhanced in either of the efflux media used. The results suggest that a principal action of AHF involves an increase in the lability and exchangeability of calcium stores. In addition to its effects in resting tissue, AHF abolished the increase in lanthanum-resistant calcium uptake induced in rat aortae by the addition of high K+ or norepinephrine to the incubation media. In a second part of the study, the effect of AHF on blood pressure and in vitro calcium uptake were compared with that of phosphatidylethanolamine (PEA), the probable identity of another endogenous antihypertensive (renin preinhibitor) compound earlier shown to share important functional similarities with AHF. The results reduce the likelihood that the two causal agents are identical. The AHF produced a significant (75 Torr, 1 Torr = 133.32 Pa) fall in the systolic blood pressure (SBP) of spontaneously hypertensive rats within 24 h following injection, whereas PEA had no effect on the SBP in this model. Both AHF and PEA reduced the resting in vitro uptake of "lanthanum-resistant" calcium in rat aortic segments. However, the AHF effect was significantly greater than PEA at each concentration studied.


2007 ◽  
Vol 34 (s1) ◽  
pp. S47-S48 ◽  
Author(s):  
Hiroko Negishi ◽  
Yuko Onobayashi ◽  
Jin-Wen Xu ◽  
Marina Alois Njelekela ◽  
Akira Kobayakawa ◽  
...  

1977 ◽  
Vol 233 (1) ◽  
pp. H141-H147 ◽  
Author(s):  
S. Baez ◽  
S. M. Feldman ◽  
P. M. Gootman

The responses to central nervous system (CNS) stimulation of consecutive segments of arterioles down to the precapillary sphincter were measured in the mesoappendix and/or cremaster of nine male rats with indwelling electrodes. Under pentobarbital sodium anesthesia, vasoactive sites were stimulated at threshold for maximal constriction or lumen closure of the precapillary sphincter and/or immediately preceding precapillary arteriole (metarteriole). In all experiments, CNS stimulation induced blood pressure elevation and constriction of three consecutive segments of precapillary vessels and of the sphincter. A threefold increase in rate of vasomotion of precapillary sphincter and metarteriole was the rule, but this was noted infrequently in larger arterioles. In addition to an overall influence of the CNS on microcirculation, the data show a gradient of responses to stimulation, the slope of which is negatively related to the size of the vessels and sphincter, in both tissues studied. A complete lumen closure of the metarteriole and precapillary sphincter (when present) in response to CNS stimulation implies active participation in the regulation of local blood flow. No evidence was foun for central neural regulation of the precapillary sphincter independent of arteriolar control.


2015 ◽  
Vol 14 ◽  
pp. 126-132 ◽  
Author(s):  
Md Alauddin ◽  
Hitoshi Shirakawa ◽  
Kazuyuki Hiwatashi ◽  
Atsushi Shimakage ◽  
Saori Takahashi ◽  
...  

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