Biomedical subjects

B G Zimmerman

Publications and source records attributed to B G Zimmerman.

At least 19 recordsLinked to original sources

PubMed1997

Angiotensin II release from rabbit intrarenal arteries: a critical assessment.

A microdissected rabbit intrarenal arterial network (IAN) perfused at constant flow with Krebs-bicarbonate solution was employed to determine whether this network, which has a high renin content, releases angiotensin II (AII) either spontaneously or during beta-adrenergic stimulation. Six groups of experiments were conducted in which samples of the vascular effluent were collected on Sep Paks before and during intraluminal infusion of L-isoproterenol (1.1 to 11 microg/min). Separation and assay of AII were by combined HPLC and RIA. For an accurate estimation of the quantity of AII released, it was important to subtract the Krebs and isoproterenol blanks, 19 and 23 pg, respectively, from the basal and isoproterenol-induced AII release. In Groups 1 and 2, AII release was determined before and during isoproterenol infusion (5.5 microg/min). Basal release of AII was insignificant in Groups 1 to 5. In Group 1, infusion of isoproterenol caused AII release from IAN before and after removal of glomeruli (glomerulectomy), but with variability between experiments. An even higher infusion rate of isoproterenol (11 microg/min) in Group 2 caused no significant AII release. Similarly, in Group 3, in which a longer collection period was imposed, isoproterenol (5.5 microg/min) failed to cause significant AII release. In Groups 4 and 5, Goldblatt hypertensive and salt-restricted rabbits, respectively, isoproterenol caused AII release, but the effect was statistically significant only in Group 4. Supplying renin substrate in Group 6 caused only a small spontaneous AII release. We conclude that under these conditions of complete isolation from the intact circulation, the IAN despite a high renin content, releases little locally generated AII.

Adrenergic beta-Agonists↗

PubMed1997

Increased kallikrein activity in the rabbit renal vasculature during low sodium intake.

1. Vascular tissue has been shown to possess a kallikrein--kinin system that may participate in the kinin-mediated increase in renal sodium excretion. As sodium deprivation has been demonstrated to increase kallikrein content in the kidney and urine we hypothesized that during low sodium intake, kallikrein should increase in the renal vasculature. 2. Kininogenase activity, reflecting kallikrein enzymatic content, was measured in a homogenate of a microdissected intrarenal arterial network (IAN) from the rabbit kidney. Kininogenase activity was determined in rabbits on a normal sodium (n = 14) or sodium-restricted (n = 9) diet. 3. Total kininogenase activity in rabbits on a normal sodium diet was 15.0 +/- 2.7 pg kinin/mg per 30 min, while it was much higher in rabbits on a sodium-restricted diet (90.7 +/- 16.5 pg kinin/mg per 30 min). Specific tissue kallikrein activity was measured by comparing the difference in kininogenase activity in homogenates treated with soybean-trypsin inhibitor (SBTI) compared with homogenates treated with SBTI and aprotinin. This difference was much larger in the sodium-restricted rabbits than in rabbits on a normal sodium diet (29.5 +/- 3.8 vs 5.1 +/- 1.7 pg kinin/mg per 30 min, respectively). 4. We conclude that the rabbit IAN produces kallikrein, which is markedly increased in response to sodium restriction. Increased kinins during sodium restriction may modulate the pressor and anti-natriuretic systems activated during negative sodium balance.

Animals↗

PubMed1997

Tissue renin-angiotensin system: a site of drug action?

In this review, we present background material that provides partial support for a tissue renin-angiotensin system (RAS). Evidence for the existence of this system relied in part on the use of drugs, which has entailed using low doses or concentrations of angiotensin-converting enzyme inhibitors, renin inhibitors, and angiotensin antagonists to block the RAS in vascular beds and in isolated arteries or organs. Other evidence for a tissue RAS has depended upon measurements of the components of the system, i.e. enzymes, substrates, and mRNAs for these proteins. All of these components were first believed to be present in the heart and blood vessels; however, it is now known that renin in the circulating blood derived from the kidney is used for the local synthesis of angiotensins. The main emphasis of the review is on the renal RAS because it is believed that the local RAS is most prominent in this organ. The renal RAS is probably involved in the long-rather than short-term regulation of renal vascular resistance and maintenance of normal blood pressure through the regulation of sodium reabsorption.

Angiotensin II↗

PubMed1996

Kinin-mediated antihypertensive effect of captopril in deoxycorticosterone acetate-salt hypertension.

On the basis of evidence suggesting the activation of the kallikrein-kinin system in steroid-induced hypertension, we considered the possibility that the angiotensin-converting enzyme inhibitor captopril would lower the arterial blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertensive rats through kininase II inhibition. In conscious DOCA-salt hypertensive rats with intact kidneys (n = 6) or uninephrectomized rats (n = 5), the short-term administration of captopril (8 mg/kg IV) decreased mean blood pressure from 141 +/- 3 to 118 +/- 3 mm Hg (P < .05) and from 176 +/- 12 to 158 +/- 15 mm Hg (P < .05), respectively. The maximal effect of captopril was manifested between 40 and 50 minutes after its administration, and blood pressure remained depressed for at least 2 hours. The bradykinin B2 receptor antagonist Hoe 140 (500 micrograms/kg IV) abolished the antihypertensive effect of captopril in the DOCA-salt hypertensive rats, indicating kinin involvement. Losartan, an angiotensin type 1 receptor antagonist, had no effect on blood pressure in another group of DOCA-salt hypertensive rats (n = 9) and did not significantly change the response to captopril. No effect of the angiotensin-converting enzyme inhibitor was seen in normotensive control rats (n = 5), indicating the absence of a nonspecific hypotensive action of the drug. Plasma renin activity was lower in the DOCA-salt hypertensive rats (0.7 +/- 0.2 ng angiotensin I/mL per hour, n = 4) than in normotensive control rats (8.8 +/- 1.7, n = 4). The involvement of kinins in the antihypertensive effect of captopril in DOCA-salt hypertension supports the contention that the kallikrein-kinin system contributes to blood pressure regulation in this hypertension model.

Angiotensin II↗

PubMed1995

Angiotensin II-mediated renal vasoconstriction amenable to alpha 1-adrenoceptor blockade.

Renal adrenergic interactions of intravenously and intrarenal arterially administered angiotensin II were studied in the anesthetized rabbit. Systemic arterial blood pressure and left renal blood flow were monitored. Bolus doses of angiotensin II, 50 and 100 ng/kg given intravenously, caused an immediate reduction in renal blood flow followed by a more sustained vasoconstrictor response. Prazosin, 5 micrograms/kg/min, infused intrarenal arterially, decreased both components of the reduced renal blood flow, suggesting adrenergic contribution to the response. Renal denervation reduced significantly the immediate response to angiotensin II without affecting the sustained response; administration of prazosin after denervation caused a further decrease in the response. Left adrenalectomy had no significant effect on the angiotensin II-induced renal blood flow response, ruling out the possible contribution of adrenal catecholamine release via the adrenal rete. In animals that had undergone renal denervation and left adrenalectomy, the renal blood flow response to intrarenal arterial injection of subpressor doses of angiotensin II (5 and 10 ng/kg) was reduced by the infusion of prazosin. It is concluded that angiotensin II-induced renal vasoconstriction is contributed to by adrenergic actions dependent in part on intact renal nerves, but also by a component not requiring an intact nerve supply.

Adrenalectomy↗

PubMed1995

Intrarenal arterial network renin content and inhibition by EMD 58265.

The renin content, expressed as nanograms of angiotensin I/hour/milligram, of a rabbit intrarenal arterial network (IAN) was compared to that of renal cortical samples from the same animal. Tissues from six rabbits were studied. Cortical tissue (RC) and an IAN with some glomeruli and attached arterioles (IAN + glomeruli) were prepared from one kidney, and an IAN freed of glomeruli (IAN - glomeruli) was obtained from the opposite kidney. These tissues were homogenized and the supernatant incubated at pH 7.4 and 37 degrees C for 30 to 60 min or 3 to 6 h. Angiotensin I was generated in a linear fashion, and the values averaged for the two incubation periods were 844 +/- 266, 121 +/- 39, and 32 +/- 11 ng/h/mg for RC, IAN + glomeruli, and IAN - glomeruli, respectively. A specific renin inhibitor, EMD 58265, at 1 x 10(-8) mol/L attenuated and at 5 x 10(-8) mol/L almost totally abolished angiotensin I production. The results indicate that small arteries comprising the IAN contain renin, and that the enzymatic activity is most likely due to that protein and not another aspartyl protease.

Animals↗

PubMed1995

Threshold sodium excretory and renal blood flow effects of angiotensin converting enzyme inhibition.

OBJECTIVE: To probe the potential influence of a high renal tubular level of angiotensin II on sodium reabsorption using angiotensin converting enzyme inhibitors and a non-peptide angiotensin antagonist. METHODS: Systemic arterial blood pressure, renal blood flow (RBF) and electrolyte and urinary excretion were measured in anesthetized uninephrectomized Wistar rats. Captopril (n = 12), ramiprilat (n = 10) or EXP 3174 (n = 9) was infused into the renal artery in graded doses to examine whether the threshold dose that increased RBF was lower than that which increased sodium excretion rate (Na+ excretion rate). RESULTS: Whereas ramiprilat (0.5-4 micrograms/kg/min intra-arterially) and EXP 3174 (0.5-4 micrograms/kg/min intra-arterially) decreased blood pressure in all but the lowest dose of 0.5 micrograms/kg/min, captopril (1-8 micrograms/kg/min intra-arterially) did not change blood pressure except for a slight effect with the two higher doses. These three agents increased RBF to about the same degree, between 6% and 18%, which was relatively large compared with the maximal vasodilator response achievable in the kidney with acetylcholine (30-37%). Captopril given intra-arterially had a more consistent effect on Na+ excretion rate than either ramiprilat or EXP 3174. An increase in Na+ excretion rate occurred with captopril ranging from 44% to 78%, whereas no significant change was obtained with the other drugs. The dose of captopril that increased RBF was the same as that which increased Na+ excretion rate. In those experiments in which ramiprilat resulted in an increase in Na+ excretion rate (five of 10 experiments), the effective dose was the same as that which increased RBF. CONCLUSION: When administered by the intra-arterial route, captopril was more effective in increasing Na+ excretion rate than either ramiprilat or EXP 3174. Although the threshold dose of captopril and ramiprilat required to increase Na+ excretion rate and RBF was similar, suggesting blockade of a common angiotensin II pool, there was not a good correlation between these two effects.

Angiotensin II↗

PubMed1994

Comparison of renal hemodynamic effect of ramiprilat to captopril; possible role of kinins.

The purpose of this study was to compare a lipophilic angiotensin-converting enzyme (ACE) inhibitor, ramiprilat, to the hydrophilic agent, captopril, with respect to its efficacy in decreasing blood pressure (BP) and increasing renal blood flow (RBF). Fifty-seven anesthetized rabbits were instrumented for monitoring BP and RBF. Separate groups of experiments were conducted in which the inhibitors were given i.v. and intrarenal i.a. In Group I, ramiprilat (1 mg/kg and 0.5 mg/kg/hr i.v.) and captopril (2 mg/kg and 1 mg/kg/hr i.v.) decreased BP and increased RBF to the same extent. Both ACE inhibitors abolished the pressor effect and greatly attenuated the renal vasoconstrictor response to exogenous angiotensin I. When the ACE inhibitors were administered in graded doses i.a. (Group II), they caused a similar increase in RBF and decrease in BP as when given i.v. Ramiprilat was about twice as potent as captopril by either route of administration. In the presence of an i.a. infusion of the bradykinin antagonist HOE 140 (Group IV), the effect of ramiprilat and captopril given i.a. on BP and RBF was not different than in Group II. In Group V, the angiotensin II receptor antagonist, losartan, decreased BP and increased RBF. There was little further effect on RBF seen with ramiprilat, but captopril caused some additional renal vasodilatation after losartan. A small further fall in BP was obtained with both agents after losartan. In conclusion, ramiprilat and captopril, despite marked solubility differences, produced a similar renal hemodynamic effect and decrease in BP. No significant difference was seen in the presence of bradykinin antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Nitric oxide participation in renal hemodynamic effect of angiotensin converting enzyme inhibitor lisinopril.

Nitric oxide (NO) contribution to the renal hemodynamic effect of lisinopril was assessed in anesthetized rabbits. NG-Nitro-L-arginine (NArg), slightly decreased renal blood flow following vehicle. Also, NArg reversed partially the increase in renal blood flow caused by DuP 753, and almost completely reversed the effect of lisinopril. The results suggest that NO plays an important role in the renal hemodynamic effect of lisinopril, more so than its contribution to the effect of DuP 753.

Amino Acid Oxidoreductases↗

PubMed1992

Method for study of endothelium-dependent vasodilatation in rabbit intrarenal arterial network.

The objectives of this study were twofold: 1) to determine whether a microdissected rabbit intrarenal arterial network (IAN), consisting mainly of interlobar, arcuate, and interlobular arteries exhibits endothelium-dependent vasodilatation, and 2) to establish a means of selectively abolishing this response. The IAN was perfused at a constant flow with heated-oxygenated Krebs-bicarbonate buffer through the main renal artery, and evoked responses were limited to vessels distal to the renal artery. A decrease in perfusion pressure reflected a vasodilator response, after vascular tone had been induced by intraarterial infusion of phenylephrine. Bolus injections of acetylcholine produced graded endothelium-dependent vasodilator responses, whereas glyceryl trinitrate caused endothelium-independent responses. Manual de-endothelialization was accomplished by gently stroking the IAN and at the same time removing any remaining glomeruli. This procedure blocked the response to acetylcholine, but not to glyceryl trinitrate (n = 6). A 10-min infusion of NG nitro-L-arginine (NArg) (4 x 10(-5)-3 x 10(-4) M) into the IAN also selectively attenuated the response to acetylcholine (n = 7). The third procedure, consisting of a 10-min infusion of 22-44 mM hydrogen peroxide into the IAN also attenuated the response to acetylcholine, but not to glyceryl trinitrate in nine of 12 experiments. This investigation demonstrates that intrarenal arteries are capable of undergoing endothelium-dependent vasodilatation, and the potential use of the IAN for further study of renal endothelium-derived vasoactive factors.

Acetylcholine↗

PubMed1992

Renal hemodynamics in canine DOCA-salt hypertension: effect of calcium channel blockade.

Systemic arterial blood pressure (BP), renal blood flow (RBF), and renal vascular resistance (RVR) were followed for 3-4 wks during the progression of DOCA-salt hypertension in the conscious dog. Accompanying the gradual increase in BP was an increase in RBF; however, RVR was unchanged. The hypertension was totally reversed 5-7 days after cessation of DOCA-salt treatment, but the increase in RBF persisted, presumably as a result of renal hypertrophy. Renal adrenoceptor blockade with prazosin (6 dogs) and prazosin plus idazoxan (4 dogs) caused a comparable decrease in BP in the normotensive and DOCA-salt hypertensive dog; however, RVR was decreased only in the normotensive. Similar results were obtained during ganglionic blockade with hexamethonium. The i.v. infusion of diltiazem for 1 wk restored BP of the hypertensive dog to a normotensive level, and hexamethonium given i.v. had little further effect on either BP or RVR. These results suggest a non-neurogenically mediated mechanism of canine DOCA-salt hypertension that is susceptible to calcium channel blockade.

Adrenergic alpha-Antagonists↗

PubMed1992

Relation between inhibition of renal angiotensin II production and hemodynamic effect of captopril in anesthetized rabbit.

OBJECTIVE: This study was conducted in order to determine the relation between the renal hemodynamic effect of an angiotensin converting enzyme (ACE) inhibitor and its effect upon plasma angiotensin II levels in the rabbit. DESIGN: The effect of captopril upon arterial and renal venous plasma angiotensin II concentrations was assumed to reflect the systemic and renal actions of ACE inhibition. METHODS: Systemic blood pressure, renal blood flow (RBF), and arterial and renal venous plasma concentrations of angiotensin II and angiotensin I were measured in five groups of anesthetized rabbits; groups Ia and Ib consisted of sodium-replete and group II sodium-deplete rabbits in which captopril was administered in a maximal ACE inhibiting dose of 2 mg/kg, intravenously, followed by an intra-arterial (group Ia) or an intravenous (group Ib) infusion of 1 mg/kg per h; group III consisted of sodium-replete rabbits given a low captopril dose of 10 micrograms/kg per min, intra-arterially; and group IV represented control levels. In a separate group of rabbits (group V) the effects of a low dose of 10 micrograms/kg per min captopril in the presence of the angiotensin II antagonist DuP 753 were studied. RESULTS: The high dose of captopril decreased blood pressure and increased RBF in both sodium-replete and sodium-deplete rabbits. Arterial and renal venous angiotensin II levels were low in group Ia compared with groups Ib and II; however, in all three groups angiotensin II levels were markedly decreased during high-dose captopril administration. The low dose of captopril caused approximately the same increase in RBF, despite no change in angiotensin II levels. Angiotensin I concentrations tended to increase during high-dose captopril administration due to blockade of negative feedback of renin release. A time trend did not account for the results, since blood pressure, RBF and angiotensin II were stable over a 1-h period in control experiments. CONCLUSION: These results suggest that different pools of renal angiotensin II may exist, and that a small critically located pool, possibly in the endothelium, may be important in renal vascular control.

Angiotensin I↗

PubMed1992

Enhanced blood pressure and renal hemodynamic effect of chronic versus acute lisinopril administration in the rabbit.

This study was aimed at evaluating the factors responsible for the marked renal hemodynamic effect of 6-day treatment with lisinopril. Blood pressure (BP) and renal blood flow (RBF) were monitored in six groups of rabbits. Animals treated with lisinopril for 6 days (Group I) had lower BP (77 +/- 3 mm Hg) than normal controls (Groups II/III, 106 +/- 3 mm Hg, P < .05) or those given lisinopril acutely (Group IV, 93 +/- 8 mm Hg, P < .05). In addition, RBF was higher in Group I (81 +/- 2 ml/min) than in Groups II/III (54 +/- 5 ml/min, P < .05) or Group IV (66 +/- 8 ml/min, P < .05). Intrarenal arterial infusion of a B2 bradykinin receptor antagonist, D-Arg-O-[Hyp-3-Thi-5,8-D-Phe-7]bradykinin, had no effect on either BP or RBF in Group I. Administration of lisinopril for 6 days also resulted in attenuation of the vasoconstrictor responses to renal nerve stimulation (Group V). Intravenous infusion of D-Arg-O-[Hyp-3-Thi-5,8-D-Phe-7]bradykinin had no effect on the responses to nerve stimulation in lisinopril-treated rabbits (Group V) or their controls (Group VI). Moreover, D-Arg-O-[Hyp-3-Thi-5,8-D-Phe-7]bradykinin given i.v. did not alter the BP or RBF in Groups V and VI. The results indicate that angiotensin converting enzyme inhibition over a 6-day period is more effective than acute inhibition in lowering BP and dilating the renal vascular bed. The use of bradykinin antagonists did not indicate kinin involvement in the long-term effect of lisinopril on BP and RBF.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1991

Kinin contribution to renal vasodilator effect of captopril in rabbit.

This study was conducted to examine the role of bradykinin in the persistence of the renal vasodilator effect of captopril during angiotensin II receptor blockade. Blood pressure and renal blood flow were monitored in eight groups of pentobarbital-anesthetized rabbits. In group 4, captopril alone was administered, and it decreased blood pressure by 14 +/- 4 mm Hg and increased renal blood flow by 21 +/- 4 ml/min. After a bolus injection and a constant intravenous infusion of the imidazole derivative angiotensin II receptor antagonist DuP 753 (group 5), captopril decreased blood pressure by 9 +/- 2 mm Hg and increased renal blood flow by 8 +/- 1 ml/min (12 +/- 1% change in renal blood flow, p less than 0.05 versus group 4). In the presence of a constant intravenous infusion of saralasin (group 6), captopril decreased blood pressure by 13 +/- 5 mm Hg and increased renal blood flow by 7 +/- 2 ml/min (17 +/- 5% change in renal blood flow, p less than 0.05 versus group 4). These results did not differ from those in group 5. During a constant intrarenal arterial infusion of a B2 bradykinin receptor antagonist, DArg0, [Hyp3-Thi5,8-DPhe7]-bradykinin (BkA) (group 7), captopril decreased blood pressure by 14 +/- 4 mm Hg and increased renal blood flow by 10 +/- 4 ml/min. Combined administration of DuP 753 intravenously and BkA intra-arterially (group 8) eliminated the effect of captopril. In group 8, captopril caused insignificant changes in blood pressure and renal blood flow. The results indicate that DuP 753 and saralasin antagonize the renin-angiotensin system to a comparable extent in vivo. Although blockade of the latter system accounted for a significant part of the increase in renal blood flow caused by captopril, the remaining component was contributed by endogenous bradykinin.

Angiotensin II↗

PubMed1991

Beta-adrenergic-induced local angiotensin generation in the rabbit hind limb is dependent on the kidney.

Evidence was sought for beta-adrenergic-induced increase in femoral vascular angiotensin production in sham-operated and nephrectomized rabbits. Systemic blood pressure and right femoral blood flow were monitored in anesthetized rabbits. Arterial and femoral venous plasma angiotensin II (Ang II) and angiotensin I (Ang I) were measured by radioimmunoassay after high-performance liquid chromatography. Isoproterenol, 1 and 10 nmol/min, was infused intrafemoral arterially, reducing femoral vascular resistance by 47 +/- 5% and 60 +/- 6% in the sham-operated group, and by 50 +/- 6% and 63 +/- 4% in the nephrectomized group, respectively. The hemodynamic effect of isoproterenol was blocked by 2 mumol/kg propranolol injected intravenously plus 0.2 mumol/min infused intrafemoral arterially, indicating that the effect was beta-adrenergically mediated. In the sham-operated group, arterial Ang II and Ang I levels were increased, respectively, by 85 +/- 16% and 103 +/- 23% with the low dose of isoproterenol, and by 121 +/- 13% and 563 +/- 126% with the high dose of isoproterenol. The apparent femoral Ang II secretion rate was increased by 3.2-fold and 4.4-fold, and the apparent femoral Ang I secretion rate increased by 4.3-fold and 21.2-fold, with the low and high dose of isoproterenol, respectively. Propranolol abolished or markedly attenuated the increased arterial angiotensin levels and the increased femoral angiotensin secretion rates. Neither the low nor the high dose of isoproterenol caused any increase in plasma levels or the apparent femoral secretion rates of the angiotensins in the nephrectomized group. Low plasma levels of Ang I and Ang II remained in the nephrectomized group, representing some locally generated angiotensins.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗

PubMed1990

Abolition of long-term vascular influence of renin-angiotensin system.

Rabbits were bilaterally nephrectomized for 24 h or received an angiotensin-converting enzyme (ACE) inhibitor chronically (5 days) before an acute experiment. Conductance responses to sympathetic nerve stimulation (SNS) (0.25, 0.75, and 2.25 Hz) and norepinephrine (NE) administration (0.2, 0.6, and 1.8 micrograms ia) were determined from simultaneous blood pressure and iliac blood flow measurements. Conductance responses to SNS were significantly reduced in nephrectomized (44, 26, and 20%) and chronic ACE inhibition (39, 31, and 24%) groups compared with normal controls, whereas conductance responses to NE were unchanged. Continuous infusion of angiotensin II (ANG II) for 24 h restored the depressed responses to SNS in nephrectomized and chronic ACE inhibition groups compared with normal controls but did not change conductance responses to NE. Acute ACE inhibition did not affect the conductance responses to SNS or NE compared with controls. Vascular tissue ACE activity was inhibited to a similar degree (50%) in both acute and chronic ACE inhibition groups compared with normal rabbits. Sodium depletion increased the conductance responses to SNS (30 and 24% at 0.25 and 0.75 Hz, respectively), but responses to NE were not affected. Chronic ACE inhibition significantly attenuated the conductance responses to SNS and slightly decreased responses to NE in sodium-depleted rabbits. Thus, in the anesthetized rabbit, the renin-angiotensin system potentiates the effect of SNS, presumably by ANG II acting at a prejunctional site, and this effect of ANG II appears to be long term in nature. Therefore, the renin-angiotensin system exerts a physiological role in the control of blood pressure in addition to the ability of this system to support arterial pressure in pathophysiological states.

Angiotensin II↗

PubMed1990

In vivo comparison of renal and femoral vascular sensitivity and local angiotensin generation.

Experiments were conducted to compare the relative importance of the local renin-angiotensin systems in the rabbit renal and femoral vascular beds and their functional role in hemodynamic regulation. Angiotensin I (Ang I) (0.15 microgram/kg i.v.) elevated mean arterial blood pressure by 18 +/- 1 mm Hg in the renal experimental group and 19 +/- 1 mm Hg in the femoral experimental group; it decreased renal blood flow by 35 +/- 3% but increased femoral blood flow by 31 +/- 8%. All these effects were blocked by intravenous administration of captopril (2 mg/kg bolus injection plus 1 mg/kg/hr). Captopril also lowered mean arterial pressure by 17 +/- 3 and 16 +/- 2 mm Hg in the renal and femoral experimental groups, respectively, and it increased renal blood flow by 32 +/- 10% but reduced femoral blood flow by 21 +/- 4%. As a result, renal vascular resistance was decreased by 36 +/- 5%, but femoral vascular resistance remained unchanged. After captopril, plasma angiotensin II (Ang II) levels were decreased and Ang I levels increased in the two groups. The renal venous-arterial difference of Ang I was increased by captopril, but the femoral venous-arterial difference of Ang I was not, suggesting greater generation of Ang I in the kidney. In a separate group of bilateral nephrectomized rabbits, plasma Ang II levels as well as mean arterial pressure, femoral blood flow, and femoral vascular resistance were not changed by intravenous administration of captopril.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗

PubMed1990

Contractility of intrarenal arteries in Goldblatt hypertensive rabbits.

The present investigation contractile responses of microdissected intrarenal arcuate arteries from sham-operated rabbits and two-kidney, one clip Goldblatt hypertensive rabbits at 2 and 12 weeks after procedure. Arcuate arteries from both kidneys of the sham-operated rabbits and stenotic and nonstenotic kidneys of the Goldblatt hypertensive rabbits were studied. Mean arterial blood pressures of the sham-operated and Goldblatt hypertensive rabbits were 72 +/- 2 and 85 +/- 2, and 130 +/- 3 and 125 +/- 4 mm Hg at 2 weeks and 12 weeks, respectively. In vitro isometric contractile force measurements were made with a small-artery myograph. Responses to graded concentrations of norepinephrine were evoked in the arcuate arteries, and the maximum active force was developed and -log EC50 was determined. At 2 weeks after procedure, the maximum responses of the vessels from the left kidney of the sham-operated rabbits and those from the stenotic left kidney of the Goldblatt hypertensive rabbits did not differ. The responses of the vessels from the right kidney of the sham-operated rabbits did not differ from those of the nonstenotic right kidney of the hypertensive rabbits. A markedly depressed maximum response of the vessels from the nonstenotic kidney of the hypertensive as compared with the right kidney of the sham-operated rabbits was found at 12 weeks after procedure, whereas the vessels from the stenotic kidney of the hypertensive and the left kidney of the sham-operated rabbits exhibited almost identical maximal responses. Responses to U 46619 were similarly affected in the two groups of rabbits. Cold-induced contractile responses of the arcuate arteries from the nonstenotic kidney of the hypertensive rabbits did not differ from those of the sham-operated rabbits at the 12-week interval.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗