摘要:

The role of angiotensin II (All) in pressor hyperresponsiveness was examined in conscious one-kidney, one clip rabbits with renal artery stenosis 01-days' duration (renal prehyper-tensive rabbits)). Conscious one-kidney rabbits without renal artery stenosis served as controls. Two experiments were performed. The first experiment used four groups of six rabbits each, to examine the pressor responses to intravenous (i.v.) infusions of norepinephrine (NE) at several doses, ranging from 25 to 1200 ng/min/kg body weight, in -day renal artery stenosis and in -day control rabbits, receiving NE plus the - enzyme inhibitor, captoprii (SQ 14,225), or receiving NE alone. The arterial pressure and values for plasma renin activity (PRA) were the same in the renal artery stenosis rabbits as in the controls. The exaggerated pressor responses to NE in the renal artery stenosis rabbits were restored to normal by captoprii administration.The second experiment investigated the pressor responses to i.v. infusions of NE at 800 ng/min/kg in six rabbits with renal artery stenosis and in six control rabbits before captoprii, during captoprii administration, and during the administration of captoprii plus the i.v. infusion of All at 0.5,1.0, and 2.0 ng/min/kg body weight. Plasma concentrations of All were determined at each point in this experiment. The renal artery stenosis rabbits had the same values for arterial pressure and PRA as the control rabbits. The renal artery stenosis rabbits had increased pressor responses to NE, and this pressor hyperresponsiveness was abolished by captoprii. The i.v. infusion of All during captoprii treatment in the renal artery stenosis rabbits increased the pressor responses to NE, and All infusion at 2.0 ng/min/kg completely restored the pressor hyperresponsiveness in these rabbits. The control rabbits had no changes in the pressor responses to NE with captoprii or with captoprii plus any of the AH doses. Before captoprii, the control and renal artery stenosis rabbits had the same plasma concentrations of AH. With captoprii, plasma concentrations of All in the renal artery stenosis rabbits decreased to undetectably low levels and remained so during the infusions of AH at all doses. This study provided strong evidence that plasma All plays an important role in the enhanced pressor responses to NE in -day renal artery stenosis rabbits, and that this effect is not due to elevated plasma levels of All.

ISSN:0194-911X    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

The present study was designed to determine whether renal prostaglandins are in-volved in the renal vasodilation evoked by angiotensin II inhibition in sodium depletion. The convert-ing enzyme inhibitor (CEI) captopril was administered to sodium-depleted control dogs and sodium-depleted dogs that had previously received the inhibitors of prostaglandin synthesis, indomethacin or meclofenamate. CEI in control dogs increased renal blood flow (RBF) from a mean value of 220 to 309 ml/min (p<0.01) and decreased renal vascular resistance (RVR) from 0.64 to 0.38 arbitrary resistance units (ru) (p<0.01). Renal venous prostaglandin E2(PGE2) concentration also increased from 52 to 85 pg/ml (p <0.01). In the dogs that received inhibitors of prostaglandin synthesis, RBF fell from 214 to 168 ml/min (p<0.01), RVR increased from 0.61 to 0.82 ru (p<0.05), and renal venous PGE2fell from 114 to 20 pg/ml.(p<0.01). The subsequent administration of captopril increased RBF from 168 to 221 ml/min (p<0.01), lowered RVR from 0.82 to 0.43 ru (p<0.01), but failed to significantly increase renal venous PGE2(20 to 25 pg/ml). The decrease in RVR induced by captopril was not significantly different in the control dogs and in the dogs with prostaglandin synthesis inhibition. However, in the control dogs RBF after captopril was significantly higher than during the control period; this was not the case in the dogs with prostaglandin synthesis inhibition. RBF after captopril and prostaglandin inhibition was not significantly different from RBF during the control period. The results indicate that the acute renal vasodilator effect of captopril in sodium depletion does not require renal prostaglandins; however, the level of RBF after captopril is dependent upon renal prostaglandins, suggesting that endogenous prostaglandins increase renal blood flow when angiotensin II is inhibited. The results confirm previous studies indicating that captopril increases renal PGE2synthesis.

ISSN:0194-911X    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

In rats between the ages of 4 and 12 or 14 weeks, repeated daily subcutaneous adminis-tration of arachidonate (AA) at a dose of 50 or 200 mg/kg significantly retarded the development of hypertension in spontaneously hypertensive rats (SHR) but did not alter the normal age-related increase in blood pressures (BP) of normotensive (WKY) rats. Heart rates (HR) and plasma levels of norepinephrine (NE), but not epinephrine, were lower in AA-treated SHR than in saline-treated animals. AA-treated SHR and WKY gained less weight than the saline-treated controls. In pithed AA-treated SHR, stimulation of the sympathetic outflow (50 V, for 1 minute at 0.3 or 3.0 Hz) and intravenous administration of NE (0.3 or 3.0 g/kg) evoked smaller pressor responses than in saline-treated controls, but the stimulation-evoked increases in plasma catecholamines were unchanged by AA treatment. These results indicated that, in SHR, chronic AA treatment reduces BP by mechanisms that do not directly affect NE release from sympathetic nerves. There appears to be both reduced central nervous system activation of the sympathetic outflow and diminshed responses to peripheral sympathetic stimulation and exogeneous NE which may be secondary to the reduced vascular hyper-trophy that usually accompanies the development of high BP in SHR.

ISSN:0194-911X    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

Aggressive behavior in mice caused a vast release of renin into the plasma. The present data support previous findings that the main sources were the submaxillary gland and kidney. In addition, unidentified salivary glands capable of releasing renin into the saliva were demonstrated by alpha-adrenergic stimulation. The role of these glands in generating plasma renin is unknown. Experiments were performed that strongly support the possibility that aggression-provoked salivary renin may be transferred by bites from one animal to another.

ISSN:0194-911X    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

In this study a possible relationship between regulatory mechanisms involved in pain and blood pressure control has been investigated in the rat. Spontaneously hypertensive rats (SHR), their normotensive Wistar-Kyoto (WKY) controls, and two experimental models of hypertension together with their appropriate sham-operated controls were tested for their responsiveness to pain. Two methods for measurement of nociceptive responsiveness (hot plate and electric footshock thresh-old) were used. A diminished responsiveness was observed in both young (still normotensive) and adult (hypertensive) SHR. Pretreatment with naloxone reduced hot plate response times of adult SHR to the level of WKY, indicating opioid receptor involvement. Despite severe hypertension in rats with a renal artery clip and in DOCA-salt treated rats, no reduction of pain sensitivity as compared to sham-operated controls was evident in the hypertensive rats as assessed by both methods. It is concluded, that the higher pain threshold in SHR is probably determined by genetic factors rather than hyperten-sion.

ISSN:0194-911X    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

Completely inactive renin was isolated from normal human plasma by --ose column chromatography and Blue-Sepharose column chromatography. This inactive renin had a molecular weight of 54,000 daltons as determined by gel filtration on Ultrogel AcA 44. When the inactive renin was activated by trypsin, its molecular weight decreased to 48,000 daltons. The trypsin-activated renin differed from a native form of active renin in plasma with respect to molecular weight (active renin, 43,000), p1 value (active renin, 5.20; trypsin-activated renin, 5.06), km value (active renin, 60 nmoles/liter; trypsin-activated renin, 89 nmoles/liter), Ki value for pepstatin A (active renin, 2.6 μmoles/liter; trypsin-activated renin 5.0 μmoles/liter) and pH profile for angiotensin formation. Glandular kallikrein (human urinary or pig pancreatic) did not activate the inactive renin. When the trypsin-activated renin was treated with glandular kallikrein, its activity was unchanged, but its molecular and kinetic properties except pi value (trypsin-activated kallikrein-treated renin, 4.82) coincided with those of a native form of active renin in plasma. These results indicate that glandular kallikrein does not directly activate inactive renin but participates in the activation process of inactive renin. The results also suggest that inactive renin in human plasma is a renin precursor.

ISSN:0194-911X    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

The present study was designed to measure norepinephrine release during sympathetic nerve stimulation and evaluate the presynaptic inhibitory and facilitatory actions of α-adrenoceptor and β-adrenoceptor agonists respectively, in the isolated perfused kidney of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Periarterial nerve stimulation (0.25 to 32 Hz) caused a significantly greater release of norepinephrine, which was measured as total tritium overflow, in the SHR. The vasoconstrictor responses to periarterial nerve stimulation as well as to norepinephrine, angiotensin II, and barium chloride were also significantly greater in the SHR. Presynaptic actions of tramazoltne, an α2-adrenoceptor agonist, and salbutamol, a β2-adrenoceptor agonist, on norepinephrine release were determined during periarterial nerve stimulation at 2 Hz. Tramazoline (2 × 10−9to 2 × 10−7M) caused a - inhibition of - release of norepinephrine in SHR but not in WKY. While the highest concentration of tramazoline (2 × 10−7M) exerted an inhibitory action in the WKY, this effect was of lesser magnitude than that seen in SHR. Salbutamol (10−10to 10−6M) produced an increase in norepinephrine release during periarterial nerve stimulation; however, this action of the β-adrenoceptor agonist was similar in both the WKYand SHR. These results demonstrate that norepinephrine release during sympathetic nerve stimulation is significantly greater in the SHR, and this phenomenon may contribute to the maintenance of hypertension. While presynaptic β-adrenoceptor function is similar in both the WKY and SHR, presynaptic α-adrenoceptors are supersensitive in the SHR. This supersensitivity may be of physiological importance in curtailing an already greater release of norepinephrine present in the SHR.

ISSN:0194-911X    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

Prokallikrein in the kidney was partially purified with immunoaffinity and DEAE Sephadex A-50 column chromatographies, and its biochemical properties were studied in comparison to three active glandular kallikreins purified from kidney, serum, and urine of the rat. The properties of the enzyme obtained by trypsin activation of prokallikrein were identical with those of active glandular kallikreins from the kidney, serum, and urine of the rat. Apparent molecular weights of prokallikrein, - kallikrein, active renal kallikrein, and glandular kallikrein in rat serum were 38,000 and of active urinary kallikrein, 37,000. Prokallikrein fraction was activated only by trypsin, but not by acidification, pepsin, and rat urinary esterase A treatments. Renal kallikrein, purified in the presence of soybean trypsin inhibitor (SBTI), contained 85% prokallikrein, but the enzymic fraction, purified in the absence of SBTI, contained 23% prokallikrein. Prokallikrein contents of urinary kallikrein and glandular kallikrein in rat serum were 16% and 20% respectively. These results suggest that prokallikrein is produced in the kidney and activated easily by a trypsin-like enzyme. Since rat serum contains active glandular kallikrein, kallikrein in the kidney may be secreted not only into the urine, but also into the blood.

ISSN:0194-911X    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

The Wistar Kyoto strain of spontaneously hypertensive rat (SHR) has been character-ized as behaviorally hyperactive as well as hypertensive. The relationship between these two inbred traits remains uncertain, and their coexistence in the SHR has complicated studies of central nervous system mechanisms underlying the hypertensive process. A breeding program was initiated to exam-ine the possible genetic linkage of these two traits which, if separable, would allow us to develop substrains of SHR that are hypertensive without being hyperactive, or hyperactive without being hypertensive. We crossed SHR males with Wistar Kyoto, normotensive (WKY) female rats and produced F, hybrids which were then randomly inbred to produce an F2population. When tested at 12 weeks of age, F2rats exhibited the expected wide range of mean systolic blood pressures (BP), from 111 to 174 mm Hg, as determined using indirect tail plethysmography. The BP in the parental rats at the time of breeding (16 weeks) was 187 ± 4.5 mm Hg (SHR males, n = 7) and 111 ± 2.4 (WKY females, n = 7). Locomotor activity was determined in an automated activity cage in F, and F2rats at 12 weeks of age. These strains exhibited a wide range of phenotypic distribution of locomotor activity scores, and the mean scores were intermediary between those of SHR rats and WKY rats of the same age. Among individual rats of both the F, and F2hybrid strains, there was no correlation between the activity score and the level of the BP at 12 weeks of age. These findings indicated that the genes responsible for the hypertensive trait and those responsible for the hyperactivity trait were not tightly linked in the hybrid populations, suggesting that different genetic factors were involved in the transmission of each of these traits. Accordingly, it should be possible to separate the two traits by further selective, recombinant inbreeding procedures.

ISSN:0194-911X    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

As a means for increasing sympathetic activity, male weanling rats were given 8% sucrose solution to drink instead of water. After 5 weeks, systolic pressures measured with a tail-cuff method became appreciably elevated, and the elevation was verified when phasic pressures were later recorded directly from femoral catheters. Successful induction of sympathetic overactivity was con-sidered a likely explanation because sucrose-ingesting rats, compared with untreated controls, had faster heart rates and larger hypotensive responses to α-adrenergic blockade with phentolamine. Upon graded electrical stimulation of the ventromedial hypothalamus under urethane anesthesia, resulting pressor and sympathetic nerve responses were also larger in sucrose-treated rats. By contrast, pressor responses to injections of norepinephrine or tyramine were unaffected, thereby indicating that cardiovascular sensitivity had not been enhanced by sucrose ingestion. During intrave-nous glucose tolerance tests, increases in plasma insulin were consistently lower in - than control rats even though corresponding increases in plasma glucose were just transiently higher. These results support the interpretation that chronic sucrose ingestion inhibits pancreatic insulin secretion and elevates blood pressure by stimulating the ventromedial hypothalamus to increase sympathetic activity.

ISSN:0194-911X    

出版商:OVID    

年代:1983

数据来源: OVID