Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The aim of this study was to examine the pressor response of vasopressin (AVP) to an acute fall in blood pressure induced by ganglion blockade. 2. Aortic catheters were implanted in spontaneously hypertensive rats (SHR) stroke-prone SHR (SHRSP), normotensive Wistar-Kyoto (WKY), black-hooded Wistar (BHW) and Sprague-Dawley (SD) rats, aged 5-7 weeks and 7-9 months, for direct measurement of mean arterial pressure (MAP) under conscious, resting conditions. The ganglion blocking agent pentolinium was administered intra-arterially, followed by an AVP receptor antagonist specific for the pressor effect of AVP. The basal level of MAP attained with each drug was recorded. 3. In the adult SHR and SHRSP with established hypertension, acute ganglion blockade caused MAP to fall to a similar extent as in WKY, suggesting that the level of sympathetic pressor tone was similar in all three strains. Administration of the AVP antagonist alone did not affect resting MAP. During ganglion blockade, however, it caused a further reduction of MAP in WKY, SHR and SHRSP, the magnitude of which was greater in the hypertensive strains. After both drugs, the total fall in MAP and the residual MAP were significantly greater in the hypertensive rats. 4. In young rats, AVP had little effect on MAP, even during ganglion blockade. The residual level of MAP after both drugs was greater in the hypertensive strains. 5. The extent to which AVP can compensate for an acute fall in MAP increases with age and the development of hypertension. This tends to mask the loss of sympathetic mediated pressor tone after ganglion blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vasopressin compensates for acute loss of sympathetic pressor tone in spontaneously hypertensive rats. 832 28

CHF is a common, complex and life-threatening clinical syndrome. It is widely accepted that enhanced peripheral vascular tone plays a major role in the pathophysiology of CHF. Increased activity of the sympathetic nervous system is one of the most important factors responsible for the increased afterload in CHF. This increase in sympathetic activity occurs early in the course of development of CHF. Efferent sympathetic activity is distributed in a non-uniform way in CHF, with significant increases to the heart and kidney but normal activity to some other organs such as the lung. Increased renal sympathetic activity contributes significantly to altered neural haemodynamics, sodium and water retention, and modulation of the actions of other vasoactive hormones. The regional alteration in sympathetic activity may be largely responsible for the changes in resting regional blood flow to different organs in CHF and the maldistribution of blood flow that occurs during the stress of exercise. Disordered function of cardiovascular reflexes is observed in CHF and may contribute to disordered sympathetic function. In CHF there are significant interactions between the sympathetic nervous system and other humoral systems such as the renin-angiotensin system, AVP, ANP, endothelin and renal DA. The various drugs used in the treatment of CHF have different effects on sympathetic activity: digitalis and ACE inhibitors tend to suppress activity while diuretics may have the opposite effect. Following cardiac transplantation, there is a prompt return of sympathetic function towards normal, although the heart may remain significantly denervated for a long time, with gradual reinnervation. Cyclosporin therapy tends to increase sympathetic activity and this may contribute to post-transplant hypertension.
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PMID:Sympathetic dysfunction in heart failure. 848 86

This study was undertaken to estimate the role of AVP in the regulation of vascular tonus and blood pressure, at first, during hemodialysis hypotension and, secondly, in hypertensive patients with chronic renal failure (CRF). Study 1: among 12 patients with hemodialysis (HD) hypotension showing similar metabolic and endocrine changes except plasma AVP during HD, 6 who showed an increase in plasma AVP after HD were hemodynamically examined during HD. Gradual decreases in mean BP and cardiac index, and increases in systemic vascular resistance (SVR) and plasma AVP, with a slight time-delay, were observed and thereafter BP inversely showed a slight increase at the end of HD, whereas no significant change in HR was found throughout HD. However, the % change in SVR had a positive correlation with % change in plasma AVP levels (P < 0.01, r = 0.559), but not with that in plasma renin activity or plasma norepinephrine levels. Study 2: oral administration of 100 mg of AVP.V1-receptor antagonist, OPC21268, which completely inhibited the vasoconstriction induced by the exogenously administered AVP, did not show any changes in BP and HR of seven hypertensive CRF patients. However, OPC21268 results in a marked decrease in BP of one hypertensive CRF patient with congestive heart failure (CHF) and nephrotic syndrome. Therefore, in some patients with HD hypotension showing impaired SNS and RAS, AVP may play an important role in the maintenance of BP during HD, predominantly via its peripheral vasoconstrictive action. On the other hand, AVP might not aggressively participate in hypertension of CRF patients, even with relatively high levels of plasma AVP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of AVP in the regulation of vascular tonus and blood pressure in patients with chronic renal failure. 851 71

Abnormalities in renal handling of calcium, magnesium, or phosphate have been implicated in the development and/or maintenance of human hypertension. We have shown recently that renal excretion of these ions is correlated to blood pressure in Dahl salt-sensitive as well as salt-resistant rats. The present study was designed to determine whether renal perfusion pressure per se could affect excretion of these ions. Urinary excretion of calcium, magnesium, and phosphate was studied in anaesthetized Sprague-Dawley rats under basal conditions and during an intravenous infusion of angiotensin II (ANG II), vasopressin (AVP) or phenylephrine (PE). A cuff, placed around the aorta between the two renal arteries, allowed maintenance of normal perfusion pressure in the left kidney, while that in the right kidney was allowed to rise. Infusion of pressor agents raised mean arterial blood pressure to comparable levels (means +/- SE): ANG II (n = 7), before = 102 +/- 4, during = 133 +/- 3 mmHg, AVP (n = 8), before = 110 +/- 7, during = 136 +/- 5 mmHg, PE (n = 6), before = 111 +/- 6, during = 141 +/- 6 mmHg. Although there was no difference in excretion of calcium, magnesium and phosphate between the two kidneys under basal conditions, infusion of ANG II or PE induced hypercalciuria, hypermagnesiuria and hyperphosphaturia in the right kidney which was exposed to the increased arterial pressure. Such effects did not appear in the pressure-controlled left kidney. Infusion of AVP was associated with reduced excretion of calcium and magnesium, and increased excretion of phosphate, in the normotensive kidney. The response to the similarly increased renal perfusion pressure in this group was also reduced for calcium and magnesium, and enhanced for phosphate. The results indicate (1) renal excretion of calcium, magnesium and phosphate is renal perfusion pressure-dependent; the higher the renal perfusion pressure, the greater the excretion of these ions. (2) Independently of perfusion pressure, AVP can inhibit phosphate reabsorption and stimulate divalent cation reabsorption.
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PMID:Effect of renal perfusion pressure on excretion of calcium, magnesium, and phosphate in the rat. 856 1

Exposure to hypoxia (2-5 wk) results in systemic hypertension in rats and in humans. The possible mechanism(s) was investigated in rats acclimatized for 3 wk to barometric pressure of approximately 370 Torr (A) and in nonacclimatized littermates (NA) by administration of alpha-adrenergic [phentolamine (PHLM)], angiotensin II (ANG II), and arginine vasopressin (AVP V1) receptor antagonists. Both A and NA rats were studied in hypoxia (inspiratory O2 fraction = 0.10). Baseline mean arterial blood pressure (MABP) was higher in A than in NA rats: 126 +/- 4 vs. 101 +/- 2 mmHg (P < 0.05). Neither ANG II nor AVP V1 receptor antagonist influenced baseline MABP; however, both contributed to MABP recovery after PHLM. After simultaneous blockade of ANG II and AVP V1, PHLM lowered MABP by 65 +/- 2 and 45 +/- 3 mmHg in A and NA rats, respectively (P < 0.05). After combined blockade of the three systems, the smooth muscle relaxant sodium nitroprusside did not further modify MABP, which remained higher in A rats. It is concluded that 1) the hypertension in A rats is partly due to a higher alpha-adrenergic tone, 2) neither ANG II nor AVP contributes to the hypertension, but ANG II and AVP participate in MABP control after PHLM, 3) no other vasoconstrictor agents operate in either group, and 4) the higher MABP in A rats after sodium nitroprusside may reflect additional hypertensive mechanisms.
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PMID:Role of vasoconstrictors in the systemic hypertension of rats acclimatized to hypoxia. 859 26

In the past decade there have been considerable advances in basic knowledge of the renin-angiotensin system (RAS). The most important new development has been the appreciation of a tissue based RAS that can be independently regulated from the renal and vascular RAS. Greater insight into the mechanism by which angiotension-II (AII) exerts its action has been achieved through the study of molecular biology and pharmacological characterization of multiple receptor subtypes. This review summarises the features and distribution of several binding subtypes that may mediate the diverse functions of AII. Of these AT1 subtype is the most well known receptor which preferentially binds AII and AIII. The AT1 receptor site appears to mediate the classic angiotensin responses concerned with the body water balance and the maintenance of blood pressure. Less is known about the AT2 sites which also bind AII and AIII and may play a role in vascular growth. Recently, an AT3 has been discovered in cultured neuroblastoma cells and an AT4 site which preferentially binds AIV. It has been implicated in memory aquisition and retrieval and in the regulation of blood flow. Another important aspect covered is the primary and secondary messengers involved during the signal transduction after the binding of AII with receptors. A stress has also been given on the regulation of density and affinity of AII receptors by various physiological parametres as they affect the responses of RAS. Autoregulation by RAS, salt intake, development and aging and some of the hormones are important variables which could affect the AII receptors. Interactions of AII with various neuroeffector transmission involved in the regulation of water-electrolyte balance and BP regulation play an important role in the maintenance of the homeostasis. AII has been suggested to increase the NAergic transmission by enhancing synthesis, release, inhibiting reuptake by the presynaptic nerve terminals as well as enhancing cell responsiveness to the transmitter. The finding of existence of AII receptors in vagal afferent nerve terminals suggests that its baroreflex inhibitory effect is mediated by inhibiting neurotransmitter release at NTS in the baroreflex arc. Moreover, AII acts on the central receptors to stimulate AVP and ACTH secretion, drinking and peripherally increase synthesis and secretion of aldosterone. Interactions of RAS with kallikrein-kinin system and prostaglandins strongly support the existence of a balance between renal depressor and pressor substances. AII is now considered a growth promotor in cardiovascular tissues and the resultant vascular hypertrophy could contribute in the maintenance of hypertension. AII also plays a role in the kidney, not only as a regulator of hemodynamics but also in the structural changes occurring in a variety of renal disorders. In addition to the more well studied functions of RAS in RVH the review also highlights the potential contribution by the RAS to other clinically relevant syndromes such as aortoarterities induced RVH, hyperaldosteronism, heavy metal induced cardiovascular effects, diabetes mellitus and thyroid dysfunction. Although the receptor subtypes involved in these pathological states have not been definitely identified, research efforts in this direction are ongoing.
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PMID:Angiotensin II--receptor subtypes characterization and pathophysiological implications. 864 21

1. We investigated the cardiovascular effects of intracerebroventricularly administered (ICV) growth hormone-releasing factor (GRF) in both spontaneously hypertensive rats (SHR) and Wistar rats (WR) with reference to the involvement of adrenergic mechanisms and plasma AVP concentration. 2. The ICV GRF induced biphasic changes of mean arterial pressure (MAP) in SHR. In the first phase, maximum pressor response was observed 2-3 min after injection. In the second phase, maximum depressor response was observed 12-13 min after injection, and lasted up to 21-22 min. In WR, there were no significant changes in MAP. 3. ICV phentolamine attenuated the GRF-induced pressor response, but did not affect the depressor response. ICV bunazosine had no effect in both responses. ICV yohimbine attenuated the GRF-induced pressor response, but did not affect the depressor response. 4. In SHR, plasma AVP concentration was not affected by ICV GRF. 5. These data suggest that central GRF plays an important role in the maintenance of hypertension in SHR, since ICV GRF caused a significant depressor effect in SHR but not in WR. ICV GRF induced biphasic changes of MAP in SHR. The pressor response was mediated through central alpha2-adrenoceptors. The depressor response was not mediated through central alpha-adrenoceptors. The depressor effect of ICV GRF was not mediated by the changes of plasma AVP concentration.
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PMID:Cardiovascular effects of intracerebroventricularly administered growth hormone-releasing factor in spontaneously hypertensive rat. 907 43

1. ATP-sensitive K+ channels (KATP) are activated either by decreased intracellular ATP content or ATP/ADP ratio during ischaemia. We examined the role of a cerebral KATP in arterial pressure regulation during acute cerebral ischaemia using SHR and WKY rats. Thirteen week old male SHR or WKY rats were anaesthetized with urethane, and arterial pressure and heart rate were recorded under an artificial ventilation. 2. Intracerebroventricular (i.c.v.) injections of glibenclamide, a specific inhibitor of KATP, elicited dose-dependent vasopressor responses in WKY with bilateral ligation of carotid arteries, whereas it caused smaller vasopressor responses in SHR than WKY. 3. Systemic administration of AVP V1 receptor antagonist, OPC-21268, abolished the vasopressor responses of i.c.v. injections of glibenclamide in WKY but not in SHR. 4. Intracerebroventricular injections of glibenclamide caused both the increase in plasma concentration of AVP and the decrease in pituitary AVP content in WKY with bilateral ligation of carotid arteries, whereas it elicited no significant change in plasma and pituitary concentration of AVP in SHR with bilateral ligation of carotid arteries. 5. Cerebral KATP may play a role in the protection of excess hypertension by inhibiting AVP release from the pituitary glands during acute ischaemia in WKY, but this mechanism might not work in SHR during acute cerebral ischaemia.
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PMID:Role of cerebral ATP-sensitive K+ channels in arterial pressure regulation during acute cerebral ischaemia in SHR and WKY rats. 907 49

We have recently characterized a novel angiotensin II/vasopressin (Ang II/AVP) dual receptor coupled to adenylate cyclase and responding with equal sensitivity to Ang II and AVP. To gain insight into putative renal physiological roles of the dual Ang II/AVP receptor, we determined its pharmacological binding properties and renal immunocytochemical distribution. The effective displacement of [3H]AVP by [1-deamino-Val14,D-Arg8]-vasopressin (DVDAVP), a specific antidiuretic AVP analogue, supports a V2-type AVP receptor characteristic of the Ang II/AVP receptor. Displacement of 125I-Ang II by losartan but not by PD 123319 defines the Ang II/AVP receptor as a novel AT1 receptor isoform coupled to adenylate cyclase, in contrast to prototype Ca(2+)-mobilizing AT1 receptors. Neither Ang II nor AVP displace each other, corroborating the predicted discrete binding domains for Ang II and AVP but presenting an enigma for the dissection of putative Ang II- and AVP-specific hierarchical roles of the dual Ang II/AVP receptor. The renal cytolocalization of the Ang II/AVP receptor to the outer medullary thick ascending limb tubules and inner medullary collecting ducts is consistent with the well-established AVP stimulation of sodium and water reabsorption in these tubules. These data suggest that the Ang II/AVP receptor might provide the molecular basis for the observed similar stimulatory effects of Ang II and AVP on renal tubular sodium and fluid reabsorption at physiological hormone concentrations.
Hypertension 1997 Apr
PMID:Renal immunocytochemical distribution and pharmacological properties of the dual angiotensin II/AVP receptor. 909 83

The levels of adrenomedullin (ADM), a newly discovered vasodilating and natriuretic peptide, are elevated in plasma and ventricular myocardium in human congestive heart failure suggesting that cardiac synthesis may contribute to the plasma concentrations of ADM. To examine the time course of induction and mechanisms regulating cardiac ADM gene expression, we determined the effect of acute and short-term cardiac overload on ventricular ADM mRNA and immunoreactive ADM (ir-ADM) levels in conscious rats. Acute pressure overload was produced by infusion of arginine8-vasopressin (AVP, 0.05 microg/kg/min, i.v.) for 2 h into 12-week-old hypertensive TGR(mREN-2)27 rats and normotensive Sprague-Dawley (SD) rats. Hypertension and marked left ventricular hypertrophy were associated with 2.2-times higher ir-ADM levels in the left ventricular epicardial layer (178 +/- 36 vs. 81 +/- 23 fmol/g, P<0.05) and 2.6-times higher ir-ADM levels in the left ventricular endocardial layer (213 +/- 23 vs. 83 +/- 22 fmol/g, P<0.01). The infusion of AVP for 2 h in normotensive rats produced rapid increases in the levels of left ventricular ADM mRNA (epicardial layer: 1.6-fold, P<0.05) and ir-ADM (endocardial layer: from 83 +/- 22 to 140 +/- 12 fmol/g, P<0.05), whereas ventricular ADM mRNA and ir-ADM levels did not change significantly in hypertensive rats. Short-term cardiac overload, induced by administration of angiotensin II (33.3 microg/kg/h, s.c., osmotic minipumps) for two weeks in normotensive SD rats resulted in left ventricular hypertrophy (3.05 +/- 0.17 vs. 2.75 +/- 0.3 mg/g, P<0.05) and a 1.5-fold increase (P<0.05) in ventricular ADM mRNA levels. In conclusion, the present results show that pressure overload acutely stimulated ventricular ADM gene expression in conscious normotensive rats suggesting a potential beneficial role for endogenous ADM production in the heart against cardiac overload. Since pressure overload-induced increase in ADM synthesis was attenuated in hypertensive rats, alterations in the ADM system may contribute to the pathogenesis of hypertension in the TGR(mREN-2)27 rat.
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PMID:Adrenomedullin gene expression in the rat heart is stimulated by acute pressure overload: blunted effect in experimental hypertension. 916 59


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