Increased levels of platelet-activating factor (1-O-alkyl-2-acetylglycerophosphocholine) in blood after reversal of renal clip hypertension in the rat

1988 ◽  
Vol 74 (4) ◽  
pp. 393-396 ◽  
Author(s):  
H. M. McGowan ◽  
R. Vandongen ◽  
L. D. Kelly ◽  
K. J. Hill

1. This study analyses whole blood in acutely unclipped one-kidney, one-clip (1K,1C) hypertensive rats for the presence of platelet-activating factor (PAF), a potent vasodilator and a putative mediator of the rapid blood pressure (BP) fall seen after unclipping. 2. Hypertensive 1K,1C rats were anaesthetized and a carotid and jugular cannula were inserted for BP measurement and anaesthetic infusion respectively. After a stable level of anaesthesia was attained, the constrictive clip was removed and BP was recorded for 30 min. 3. Blood was drawn from the aorta directly into ice-cold acetone. The extract was analysed for PAF by a bioassay using 5-hydroxy-[14C]tryptamine-labelled platelets. 4. Rats which showed a BP fall had elevated levels of PAF [55 ± 6 (sem) pg/ml] when compared with those with no fall in BP [26 ± 7 (sem) pg/ml] (P < 0.01). 5. This supports the hypothesis that activation of PAF biosynthesis may be a mechanism contributing to the fall in BP seen after unclipping the 1K,1C hypertensive rat.

1986 ◽  
Vol 251 (6) ◽  
pp. H1361-H1364 ◽  
Author(s):  
H. M. McGowan ◽  
R. Vandongen ◽  
J. P. Codde ◽  
K. D. Croft

Previous studies have implicated vasodilatory prostaglandins (PGs) in the reversal of hypertension following unclipping in the one-kidney, one-clip (1K,1C) hypertensive rat. The capacity of the aorta to synthesize prostacyclin (PGI2) was compared in clipped (group A, n = 9), unclipped (group B, n = 8 and group D, n = 9), and sham-unclipped (group C, n = 9) 1K,1C hypertensive rats. The involvement of platelet-activating factor (PAF), a potent renal antihypertensive phospholipid, in the reversal of renal clip hypertension was also examined. Hypertensive rats [systolic blood pressure (BP) greater than 180 mmHg] were fed a synthetic diet for 4 wk, after which group A was killed immediately, group C was sham-unclipped, and groups B and D unclipped and killed 24 h later. Blood was drawn for the measurement of plasma lyso-PAF (the precursor of PAF) and the aorta removed for determination of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha, the stable hydrolysis product of PGI2). BP fell substantially in the unclipped rats (groups B and D) but did not change in the sham-unclipped rats (group C). Mean aortic 6-keto-PGF1 alpha was increased in the unclipped groups [group B, 15.4 +/- 2.4 (SE) ng/mg; group D, 10.8 +/- 2 ng/mg] compared with group A (7.7 +/- 1 ng/mg) and group C (7.1 +/- 1 ng/mg) (H = 13.74, P less than 0.01). Plasma lyso-PAF was also significantly increased in the unclipped (group D, 261 +/- 26 ng/ml) vs. the sham-unclipped group (group C, 211 +/- 23 ng/ml, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


1968 ◽  
Vol 59 (2) ◽  
pp. 227-234 ◽  
Author(s):  
H. C. Moore ◽  
I. Cserhati ◽  
F. P. Biliczki

ABSTRACT Experimental deciduomata and progesterone together lower the blood pressure in the steroid hypertensive rat from the 5th to 10th day of decidual growth i. e. from the 10th to 15th day of pseudopregnancy. This would suggest that the fall of blood pressure at an equivalent time of gestation in hypertensive pregnant rats could be due to the maternal decidua under the influence of progesterone. It is further considered that the metrial gland of the deciduoma is more likely to be responsible for the hypotensive effect and by comparison that the metrial gland is implicated in the hypotensive effect of pregnancy. Progesterone alone also exerts a minor hypotensive effect in those animals in which a nephrectomy forms part of the hypertension regimen and indicates one way in which a maternal renal factor could influence blood pressure responses in hypertensive pregnant rats.


1981 ◽  
Vol 241 (5) ◽  
pp. F525-F531
Author(s):  
F. H. Leenen ◽  
W. de Jong

In two-kidney one-clip hypertensive rats we evaluated the effect of water restriction on the development and maintenance of severe hypertension (systemic blood pressure 200-230 mmHg). After application of renal arterial clips in rats allowed access to water for 1 or 2 h daily, BP stabilized at 180-190 mmHg. No increase in water intake occurred and plasma renin activity(PRA) (measured before the drinking period) was significantly below the levels observed in ad libitum-drinking hypertensive rats. In rats administered 4 ml water/100 g body weight twice daily by gavage, development of hypertension was more clearly suppressed. Blood pressure increased slowly and reached levels of only 150-170 mmHg. Furthermore, PRA was significantly lower in this group compared with ad libitum-drinking hypertensive animals. In rats with established (4-5 wk) renal hypertension, restriction of water intake to 1 or 2 h daily resulted in a rapid decrease in BP of about 30 mmHg. Daily administration of Pitressin tannate to hypertensive rats allowed free access to water induced a similar decrease in BP as well as suppression of PRA. These results indicate that the hypotensive effect of water restriction in the two-kidney one-clip hypertensive rat model may be mediated, at least in part, through elevated circulating levels of vasopressin that subsequently inhibit renin release.


Planta Medica ◽  
2020 ◽  
Vol 86 (06) ◽  
pp. 395-404 ◽  
Author(s):  
Fabiana Gomes ◽  
André M. Marques ◽  
Obadia Nathalie ◽  
Marcos Adriano Lessa ◽  
Eduardo Tibiriçá ◽  
...  

Abstract Echinodorus grandiflorus is a semiaquatic plant native to Brazil and belongs to the Alismataceae family. Infusion preparations of the leaves of this plant are often used due to its diuretic, blood pressure lowering, and anti-inflammatory properties. Our aim was to investigate the effects of chronic treatment with the crude hydroalcoholic extract of E. grandiflorus on central and peripheral microvascular changes induced in a model of hypertension and diabetes. The hemodynamic and microvascular effects of E. grandiflorus extract (50, 100, or 200 mg/kg/day for 28 days) or the isolated major diterpene from E. grandiflorus (3 to 10 mg/kg i. v.) were evaluated in spontaneously hypertensive rats using tail plethysmography and intravital fluorescence videomicroscopy, respectively, and were compared to vehicle-treated normotensive Wistar-Kyoto rats. We also investigated the protective effects of chronic treatment with E. grandiflorus (100 mg/kg/day) in brain capillary density and leukocyte-endothelium interactions on the brain vessels of DM-spontaneously (DM: diabetes mellitus) hypertensive rats. Chronically treating spontaneously hypertensive rats with increasing doses of crude hydroalcoholic E. grandiflorus extract resulted in significant dose-dependent reductions in systolic blood pressure and an anti-inflammatory effect on the brain microcirculation of DM-spontaneously hypertensive rat animals. Using laser speckle contrast imaging, we observed that intravenous administration of the major isolated clerodane diterpene metabolite (1 – 10 mg/kg) increased microvascular blood flow by 25% in spontaneously hypertensive rat skeletal muscle. The results of this study show that E. grandiflorus extracts can be useful in the prevention and reduction of microcirculatory damage in arterial hypertension and other diseases that involve microvascular dysfunction.


2000 ◽  
Vol 3 (1) ◽  
pp. 33-38 ◽  
Author(s):  
MICHAEL R. GARRETT ◽  
YASSER SAAD ◽  
HOWARD DENE ◽  
JOHN P. RAPP

Garrett, Michael R., Yasser Saad, Howard Dene, and John P. Rapp. Blood pressure QTL that differentiate Dahl salt-sensitive and spontaneously hypertensive rats. Physiol Genomics 3: 33–38, 2000.—Our purpose was to define quantitative trait loci (QTL) for blood pressure that differ between two widely used hypertensive rat strains, the Dahl salt-sensitive (S) rat and the spontaneously hypertensive rat (SHR). A genome scan was done on an F2 (S × SHR) population fed 8% NaCl for 4 wk. Three blood pressure QTL were detected, one on each of rat chromosomes (chr) 3, 8, and 9. For the chr 3 QTL the SHR allele increased blood pressure, and for chr 8 and 9 the S allele increased blood pressure. The QTL on chr 9 was exceptionally strong, having a LOD score of 7.3 and accounting for 30% of the phenotypic variance and a difference of 40 mmHg between homozygotes. A review of the literature in conjunction with the present data suggests that S and SHR are not different for the previously described prominent blood pressure QTL on chr 1, 2, 10, and 13. QTL for body weight on chr 4, 12, 18, and 20, each with an effect of about 30 g, were incidentally observed.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Soyi Park ◽  
Ki Hoon Lee ◽  
Hakjoon Choi ◽  
Goeun Jang ◽  
Wan Seok Kang ◽  
...  

Abstract Background We previously showed that enzymatically hydrolyzed Dendropanax morbiferus H. Lév. leaf (Hy-DP) and unripe Rubus coreanus Miq. (5-uRCK) extracts exhibit potent vasodilator effects on isolated aortic rings from rats partly through endothelium-dependent and endothelium-independent mechanisms. These two extracts have different mechanisms of action; however, their combined effect on antihypertensive activity has not been explored. Methods The present study aims to investigate the effect of a chronic optimized mixture (HDR-2, composed of Hy-DP and 5-uRCK in a 2:1 mass ratio) on vascular tension and blood pressure in two different hypertensive rat models. Results The results showed that HDR-2 concentration-dependently relaxed endothelium-intact and endothelium-denuded aortic rings precontracted with phenylephrine. Antihypertensive effects were assessed in vivo on a 1 kidney-1 clip (1 K-1C) rat model of hypertension and spontaneously hypertensive rats (SHRs). Acute HDR-2 treatment significantly decreased systolic blood pressure (SBP) 3 h posttreatment in both models. Chronic HDR-2 administration also significantly decreased SBP in the hypertensive rat models. Moreover, HDR-2 increased eNOS protein expression and phosphorylation levels in the aorta. Conclusion Chronic HDR-2 administration may effectively improve vascular function by decreasing plasma angiotensin-converting enzyme (ACE) activity and AngII levels. HDR-2 significantly improved acetylcholine (ACh)-induced aortic endothelium-dependent relaxation and affected sodium nitroprusside (SNP)-induced endothelium-independent relaxation in SHRs.


1995 ◽  
Vol 88 (6) ◽  
pp. 719-725 ◽  
Author(s):  
Margriet R. van der Schaaf ◽  
Jaap A. Joles ◽  
Arie van Tol ◽  
Hein A. Koomans

1. Fructose feeding, as opposed to vegetable starch feeding, has been shown to elevate blood pressure and to decrease insulin sensitivity in normotensive rats. The long-term relevance of this is unclear, and data in hypertensive strains are scarce. 2. We studied the effects of 27 weeks of a fructose-versus a corn-starch-enriched (69.5% w/w) diet in the spontaneously hypertensive rat. 3. In both dietary groups, blood pressure increased with ageing, with no apparent difference between the diets. The fructose-fed rats gained less weight. However, even selecting fructose-fed rats that matched the weight gain in the corn starch group, did not reveal a significant elevation of systolic blood pressure over time. 4. Extracellular fluid volume was comparable in fructose-fed and corn-starch-fed rats. No effects on creatinine clearance, proteinuria or renal histology were found. Fasting values of plasma triacylgycerols and cholesterol were increased mildly after 2 weeks on the fructose diet. However, fasting glucose and insulin measured after 2 weeks, and the response to an intraperitoneal glucose load, were no different. After 23 weeks of the diets, fasting values of plasma glucose, insulin, triacylglycerols and cholesterol did not differ. There were small differences in the response of plasma glucose levels to the intraperitoneal glucose load, but the area under the curve was not different. The baseline insulin resistance present in spontaneously hypertensive rats possibly blunts the metabolic response to dietary fructose. 5. After 27 weeks, the diets were switched in crossover design, and measurements were continued until 39 weeks. The fructose diet did not elevate systolic blood pressure in this follow-up experiment. 6. To summarize, long-term fructose versus corn starch feeding did not increase systolic blood pressure in spontaneously hypertensive rats. Metabolic variables were transiently affected and renal function was undisturbed. These findings suggest that long-term fructose feeding, compared with other dietary carbohydrates, is not specifically harmful in the spontaneously hypertensive rat.


2011 ◽  
Vol 300 (1) ◽  
pp. H214-H222 ◽  
Author(s):  
Melissa M. J. Farnham ◽  
Melissa A. Inglott ◽  
Paul M. Pilowsky

The rostral ventrolateral medulla contains presympathetic neurons that project monosynaptically to sympathetic preganglionic neurons (SPN) in the spinal cord and are essential for the tonic and reflex control of the cardiovascular system. SPN directly innervate the adrenal medulla and, via postganglionic axons, affect the heart, kidneys, and blood vessels to alter sympathetic outflow and hence blood pressure. Over 80% of bulbospinal, catecholaminergic (C1) neurons contain pituitary adenylate cyclase-activating polypeptide (PACAP) mRNA. Activation of PACAP receptors with intrathecal infusion of PACAP-38 causes a robust, prolonged elevation in sympathetic tone. Given that a common feature of most forms of hypertension is elevated sympathetic tone, this study aimed to determine in the spontaneously hypertensive rat (SHR) and the Wistar Kyoto rat (normotensive control) 1) the proportion of C1 neurons containing PACAP mRNA and 2) responsiveness to intrathecal PACAP-38. We further investigated whether intrathecal infusion of the PACAP antagonist, PACAP(6–38), reduces the hypertension in the SHR. The principal findings are that 1) the proportion of PACAP mRNA-containing C1 neurons is not different between normotensive and hypertensive rats, 2) intrathecal PACAP-38 causes a strain-dependent, sustained sympathoexcitation and tachycardia with variable effects on mean arterial pressure in normotensive and hypertensive rats, and 3) PACAP(6–38) effectively attenuated the effects of intrathecal PACAP-38, but had no effect alone, on any baseline variables. This finding indicates that PACAP-38 is not tonically released in the spinal cord of rats. A role for PACAP in hypertension in conscious rats remains to be determined.


1979 ◽  
Vol 56 (1) ◽  
pp. 41-46 ◽  
Author(s):  
Josephine B. Garst ◽  
S. Koletsky ◽  
P. E. Wisenbaugh ◽  
Magdalena Hadady ◽  
D. Matthews

1. Infusion of sufficient renin to raise the blood pressure of normal rats to hypertensive levels resulted in increased renin in the arterial wall. 2. Arterial wall renin and renal venous renin were normal in younger spontaneously hypertensive rats, but in older spontaneously hypertensive rats arterial wall renin was significantly increased and renal venous renin was significantly decreased. 3. Arterial wall renin in rats with either acute or chronic two-kidney Goldblatt renal hypertension was significantly increased, whereas circulatory renin was elevated in the former, but depressed in the latter. 4. Arterial wall renin may play a role in the maintenance of acute and chronic renal hypertension and also perhaps of spontaneous hypertension of long duration in older rats.


1980 ◽  
Vol 59 (s6) ◽  
pp. 79s-82s ◽  
Author(s):  
J. S. Hutchinson ◽  
A. E. Doyle

1. Neurosecretion of peptides from superfused neurohypophyses in vitro was inhibited by dopamine. 2. This inhibition was dose-dependent. 3. Intravenous injection of the dopamine agonist, bromocriptine, lowered blood pressure in spontaneously hypertensive rats within 15 min. 4. Saralasin or captopril also lowered blood pressure of spontaneously hypertensive rats, but progressively over a period of 3 h. 5. The results suggest that dopamine and angiotensin have opposite effects on the neurosecretion of vasopressin. 6. Vasopressin appears to be involved in maintenance of blood pressure in the spontaneously hypertensive rat but is apparently not the only factor.


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