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Biomedical subjects

B G Zimmerman

Publications and source records attributed to B G Zimmerman.

At least 37 records · Page 2Linked to original sources
PubMed1990

Bradykinin contribution to renal blood flow effect of angiotensin converting enzyme inhibitor in the conscious sodium-restricted dog.

We examined the relative contribution of renin-angiotensin system blockade and bradykinin potentiation to the renal hemodynamic effect of the angiotensin converting enzyme inhibitor enalaprilat in sodium-deprived dogs. Six conscious dogs instrumented for monitoring of blood pressure (BP) and renal blood flow (RBF) were employed in five groups of experiments. In group 1, enalaprilat alone was administered, and it decreased BP by -24 +/- 3 mm Hg and increased RBF by 135 +/- 15 ml/min. During a constant intravenous infusion of saralasin (group 2), enalaprilat decreased BP by -7 +/- 3 mm Hg and increased RBF by 84 +/- 7 ml/min (delta BP and delta RBF, p less than 0.01 vs. group 1 by analysis of variance). During a constant intrarenal arterial infusion of saralasin (group 3), the respective changes in BP and RBF after enalaprilat were -10 +/- 3 mm Hg and 69 +/- 12 ml/min, and these results did not differ from those of group 2. The infusion of saralasin intravenously or intrarenal arterially decreased BP slightly and increased RBF. In the presence of an intravenous infusion of a specific bradykinin antagonist, D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Phe-Thi-Arg.TFA (B5630) (group 4), enalaprilat decreased BP by -28 +/- 4 mm Hg and increased RBF by 82 +/- 24 ml/min (delta RBF, p less than 0.01 vs. group 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1989

Characterization of intrarenal arterial adrenergic receptors in renovascular hypertension.

alpha-Adrenergic receptor subtypes were investigated using [3H]prazosin, an alpha 1 selective antagonist, and the alpha 2 selective antagonist [3H]rauwolscine in a smooth muscle plasma membrane enriched microsomal fraction prepared from rabbit intrarenal arterial vasculature. Both radioligands displayed single components on Scatchard analysis. The specific binding of [3H]prazosin was of high affinity (0.54 +/- 0.04 nM) with a maximum binding capacity (Bmax) of 212 +/- 15 fmol/mg protein. The maximum number of [3H]rauwolscine binding sites was 64 +/- 4 fmol/mg of protein with a dissociation constant (Kd) of 5.60 +2- 0.27 nM. Binding of both radioligands was rapid, saturable, and specific. alpha 1- and alpha 2-adrenergic receptors in the intrarenal arterial membrane preparation were also characterized at 2-, 4-6-, and 10-12-week intervals during the course of development and maintenance of chronic two-kidney, one clip (2K1C) Goldblatt hypertension and in age-matched sham-operated normotensive control rabbits. The alpha 1-adrenergic receptor affinity for [3H]prazosin binding in hypertensive rabbits was significantly increased in the stenotic, but not contralateral, kidney at 2 weeks; however, at 6 weeks the receptor affinity of both kidneys was significantly increased compared with those of the normotensive control group. No difference in alpha 1-adrenergic receptor affinity was seen at 12 weeks, and there were no changes in Bmax at any of the weekly intervals. Neither the Kd, nor Bmax, for [3H]rauwolscine in either kidney showed a significant difference between hypertensive rabbits and normotensive control rabbits. These studies demonstrate the existence in the rabbit intrarenal arterial vasculature of binding sites with alpha 1- and alpha 2-adrenergic receptor specificity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Renal hemodynamic effects of a selected calcium antagonist.

Calcium antagonists are unique antihypertensive drugs that appear to exert selective blood pressure-lowering and possibly renal hemodynamic and functional effects in hypertensive patients and animals. There is evidence for inhibition of tubular sodium reabsorption and renal vasodilatation when certain of these agents are given by acute intravenous or intrarenal arterial administration. These renal effects have been observed to occur either independently or together. Both natriuresis and diuresis have been found to occur with these drugs. In the deoxycorticosterone-salt hypertensive dog, chronically administered diltiazem reduces blood pressure, transiently increases renal blood flow and increases urine volume. Administered either acutely or chronically to these hypertensive dogs, diltiazem depresses renal vascular reactivity. Pressor and renal vasoconstrictor responses to angiotensin II and norepinephrine are attenuated to a similar degree. The chronic blood pressure-lowering effect of diltiazem is most likely a function of depressed vascular reactivity; however, actions at other sites cannot be ruled out based on our experiments. Postprandial renal vasodilatation readily occurs in the conscious instrumented dog, and although this response is blocked by the acute administration of a calcium antagonist, the response is unaltered during the chronic administration of diltiazem.

Animals↗
PubMed1988

Postsynaptic alpha 1- and alpha 2-adrenergic mechanisms in coronary vasoconstriction.

This study examined the relative importance of postsynaptic alpha 1- and alpha 2-adrenoceptors in mediating coronary vasoconstriction in open chest dogs in which the left circumflex coronary artery was cannulated and perfused at a constant rate. The cervical vagus nerves and central connections of the stellate ganglia were transected, and beta-adrenergic blockade was produced with propranolol. Coronary vasoconstriction occurred in response to intraarterial administration of both the alpha 1-agonist phenylephrine and the alpha 2-agonist BHT 933. The response to phenylephrine was partially blocked with prazosin and nearly completely eliminated by yohimbine. The response to BHT 933 was resistant to prazosin, but almost completely blocked by yohimbine. Coronary vasoconstriction produced by norepinephrine was resistant to prazosin, but was blunted by alpha 2-adrenergic blockade with yohimbine or idazoxan. Prazosin produced some blunting of coronary vasoconstriction in response to small doses of epinephrine, while yohimbine markedly attenuated epinephrine-induced vasoconstriction at all doses used. Measurements of regional myocardial blood flow with radioactive microspheres demonstrated no transmural redistribution of perfusion during vasoconstriction produced by either alpha 1- or alpha 2 stimulation. Thus, although stimulation of both alpha 1- and alpha 2-adrenoceptors is capable of causing coronary vasoconstriction, vasoconstriction in response to norepinephrine and epinephrine is mediated principally by postsynaptic alpha 2-adrenoceptors.

Animals↗
PubMed1988

Antihypertensive and renal vasodilator effect of diltiazem in DOCA-salt hypertensive dog.

We studied the effect of an intravenous (i.v.) infusion of diltiazem (15 micrograms/kg/min) given for 1 week on several cardiovascular parameters, renal blood flow, and electrolyte and urinary excretion in chronically instrumented DOCA-salt hypertensive dogs. On the first recording session, 24 h after diltiazem infusion was started, arterial blood pressure was decreased and renal blood flow was increased by 36%. Thereafter, the blood pressure reached a normotensive level and remained at that level for the duration of the infusion in all but one dog in which the dose had to be increased on day 7. Renal blood flow was increased for 3 days and then tended to return toward control at the end of the infusion period. An increase in urine output was seen during the period of drug infusion, but no increase in sodium excretion was detected. Pressor and renal blood flow responses to norepinephrine (NE), phenylephrine, and angiotensin II were evoked before and on the last day of the diltiazem infusion. The decreases in renal blood flow produced by all three agonists and the pressor response to NE were reduced by diltiazem. These results indicate that this calcium entry blocker can reestablish blood pressure to a normotensive level in DOCA-salt--treated dogs, but that the renal vasodilator effect accompanying the blood pressure decrease is not consistently sustained.

Animals↗
PubMed1988

Renal hemodynamics and vascular reactivity in canine DOCA-salt hypertension.

Because of the potential role that the kidney may play in deoxycorticosterone acetate (DOCA)-salt hypertension, changes in renal blood flow, renal vascular reactivity, and renal adrenergic vascular tone were followed in the conscious instrumented dog. DOCA-salt was administered daily after obtaining control measurements. Systemic mean arterial blood pressure (MAP) was monitored with an indwelling catheter, renal blood flow (RBF) was measured electromagnetically using an implanted blood flow probe, and drugs were administered intrarenal arterially through an indwelling renal artery catheter. During the first week of DOCA-salt administration MAP increased from 106 +/- 3 to 118 +/- 2 mmHg and at week 2 to 123 +/- 2 mmHg (P less than 0.01). RBF increased from 275 +/- 32 to 336 +/- 34 during week 1 (P less than 0.05) and to 324 +/- 29 ml/min during week 2. The log ED50 of norepinephrine administered intra-arterially decreased from 1.66 +/- 0.114 to 1.48 +/- 0.091 and 1.41 +/- 0.067 ng/ml (P less than 0.05), and of angiotensin II from 2.58 +/- 0.072 to 2.31 +/- 0.09 (P less than 0.05) and 2.38 +/- 0.05 pg/ml, during weeks 1 and 2, respectively. There was, however, no increase in adrenergic vascular tone as determined by the change in RBF obtained with the intra-arterial infusion of alpha-adrenoceptor antagonists. These experiments indicate that RBF is not compromised in canine DOCA-salt hypertension, and renal adrenergic tone is no greater in the hypertensive than in the normotensive control period.

Angiotensin II↗
PubMed1988

Resistance to blockade by saralasin of effect of ACE inhibitors in conscious sodium-restricted dog.

Comparison of the effect of captopril and enalaprilat was made on mean systemic arterial blood pressure (BP), renal blood flow (RBF), and renal vascular resistance (RVR) of conscious sodium-replete and sodium-restricted dogs (plasma renin activity = 6.66 ng angiotensin I.ml-1.h-1). BP was decreased by -8 +/- 2 mmHg and RBF was increased by 34 +/- 12 ml/min with captopril given intravenously and by -5 +/- 2 mmHg and 28 +/- 7 ml/min with enalaprilat in sodium-replete dogs. The respective changes in BP and RBF in sodium-restricted dogs were -29 +/- 2 mmHg and 62 +/- 12 ml/min with captopril and -25 +/- 6 mmHg and 53 +/- 18 ml/min with enalaprilat. Saralasin infused intra-arterially to the kidney significantly blocked the increase in RBF seen after angiotensin-converting enzyme (ACE) inhibition in sodium-replete dogs, and reduced the increase in RBF in sodium-restricted dogs, but the latter effect was not statistically significant. A more moderate increase in plasma renin activity was established in another group of sodium-restricted dogs, and saralasin was administered intravenously instead of intra-arterially. Enalaprilat increased RBF in these dogs in the presence of a saralasin blockade (42 +/- 7 ml/min), and this effect was not significantly changed by prior administration of indomethacin (28 +/- 6 ml/min). The results suggest that blockade of the influence of the renin-angiotensin system and possibly another vasodilator mechanism, such as kinin potentiation, account for the increase in RBF after ACE inhibition in the low-sodium state.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Intrarenal converting enzyme inhibition in rabbit.

The role of the intrarenal renin-angiotensin system on the control of renal blood flow in the rabbit was pursued in this investigation. Blood pressure (BP) and renal blood flow (RBF) were monitored in New Zealand white rabbits anesthetized with pentobarbital. Control RBF and changes in RBF elicited by infusions of angiotensin I (AI) were determined by electromagnetic flowmetry. In Group 1 (n = 7), BP and RBF responses to AI infused i.a. and i.v. were evoked in the control period and the effects of a low i.a. dose of captopril to inhibit selectively renal angiotensin converting enzyme (ACE) and then a high i.a. dose to inhibit maximally renal ACE were determined. Low dose captopril depressed the RBF response to i.a. AI by 67% without an effect on the response to i.v. AI. RBF was increased by 15.0% and renal vascular resistance (RVR) was decreased by 14.4% by low dose captopril. High dose captopril had no further effect on the response to i.a. AI, but decreased the RBF response to i.v. AI by 72%. RBF and RVR were further changed by high dose captopril. In Groups 2 and 3, high dose captopril was administered after either indomethacin or saline vehicle. Captopril increased RBF, decreased RVR, and blocked responses to AI similarly whether prostaglandin synthesis was inhibited or not. The results indicate that renal vasodilation in the rabbit can be produced by selective renal ACE inhibition with a low dose of captopril, but that systemic ACE inhibition also contributes to this effect when a high dose is given.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Renal vascular reactivity to U 46619 and adrenergic agonists in Goldblatt hypertension.

Vascular reactivity of the contralateral kidney of conscious Goldblatt hypertensive dogs was studied by eliciting renal blood flow (RBF) responses to intra-arterial infusions of vasoconstrictor and vasodilator agonists in control sessions and at weekly intervals postclipping. Systemic arterial blood pressure (BP) and RBF were monitored during each recording session via an implanted catheter and electromagnetic blood flow probe, respectively. BP was maximally increased within 1 wk and remained elevated for the duration of the study. The relationship between the negative percent change in RBF (-% delta RBF) and the renal arterial plasma concentration of adrenergic agonists, angiotensin II and thromboxane mimetic (U 46619), infused intra-arterially was subjected to regression analysis, and 25 and 50% effective doses (ED25 and ED50, respectively) were calculated. Vascular sensitivity to phenylephrine and norepinephrine increased within a month or more of hypertension. Vascular reactivity to angiotensin II was unchanged. In contrast to the delayed increase in renal vascular reactivity to adrenergic agonists, enhancement of the RBF responses to U 46619 was seen within 1-2 wk. In addition, beta-adrenoceptor-mediated vasodilation appeared suppressed during hypertension. Alteration in the response of the contralateral kidney to both vasoconstrictor and beta-adrenoceptor-mediated vasodilator stimuli may contribute to renal hemodynamic changes in Goldblatt hypertension.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1987

Effect of alpha 1-adrenoceptor blockade on blood pressure and iliac vascular resistance in normotensive and Goldblatt hypertensive dogs; influence of dietary salt and DOCA-salt.

Instrumented normotensive and two-kidney, one clip Goldblatt hypertensive dogs were placed on normal salt, high salt and DOCA-salt regimens and the effect on mean arterial blood pressure (MAP) and iliac vascular resistance (IVR) determined. High salt and DOCA-salt did not alter these variables in the Goldblatt hypertensive group. DOCA-salt increased MAP in the normotensives by 12 mmHg; however, IVR was not significantly increased by this treatment. In order to determine the degree of sympathetic tone in the iliac vascular bed, the change in IVR evoked by the alpha 1-adrenoceptor antagonists, urapidil and prazosin, was assessed. There were similar reductions in MAP and IVR after alpha 1-blockade in both groups of dogs, regardless of the salt regimen. However, urapidil caused a greater decrease in MAP in the normotensives than in the hypertensives. Captopril administration after alpha 1-blockade caused further reductions in MAP and IVR in the hypertensives, and in the MAP of the normotensive dogs on normal or high salt, indicating that the renin-angiotensin system maintained blood pressure in these groups. These results suggest that sympathetic tone is not increased by high salt- or DOCA-salt in normotensive or Goldblatt hypertensive dogs for the 8-11 day duration of these treatments.

Adrenergic alpha-Antagonists↗
PubMed1986

Beta 1-adrenoceptor antagonism by urapidil prior to and after the alpha 2-antagonist rauwolscine in anesthetized dogs.

The purpose of this investigation was to evaluate the in vivo beta-adrenoceptor antagonistic properties of urapidil, a new antihypertensive alpha 1-adrenoceptor blocking agent. In dogs anesthetized with pentobarbital, the cardioaccelerator nerve was isolated, decentralized and stimulated electrically to elicit adrenergically mediated increases in heart rate. Dobutamine was administered (3-30 micrograms/kg i.v.) to elicit increases in heart rate by the direct stimulation of beta-adrenoceptors. Urapidil 2 mg/kg i.v. had no significant effect on cardioaccelerator nerve-induced tachycardia, but 5 mg/kg i.v. decreased the response by 27%. Heart rate responses to dobutamine were suppressed slightly by the low dose of urapidil and to a greater degree by the high dose of urapidil, whereas the pressor response to dobutamine was markedly attenuated at both dose levels. Neurally or dobutamine-elicited tachycardia remaining after urapidil treatment was eliminated by propranolol (1 mg/kg i.v.). When the selective alpha 2-antagonist rauwolscine was administered (1000 micrograms/kg i.v.), tachycardic responses to nerve stimulation increased 49% above control, and urapidil (5 mg/kg) given subsequently, caused a 48% reduction in the response. These data indicate that urapidil has weak beta 1-blocking activity more clearly seen after blockade of alpha 2-adrenoceptors.

Animals↗
PubMed1986

Analysis of influence of extra- and intrarenally formed angiotensin II on renal blood flow.

Previous studies have indicated that intrarenal converting enzyme (CE) inhibition had no influence on renal blood flow (RBF). The present study examined the effect of intrarenal CE inhibition with captopril on the distribution of left (L) RBF in the anesthetized rabbit. Systemic arterial blood pressure and LRBF were measured in pentobarbital anesthetized rabbits, the latter by electromagnetic flowmetry. Radiolabeled 15-mu microspheres (85Sr and 141Ce) were used to determine RBF distribution. A dose of captopril that blocked the LRBF response to angiotensin I (ANG I), 0.3 microgram/kg/min i.a., but had no effect on the response to ANG I i.v. was established. Captopril administered i.a. at 0.2 microgram/kg/min for 20 min into the left renal artery decreased the response to ANG I i.a. by 71% without any effect on the response to ANG I i.v. The deep to superficial cortical blood flow ratio was unaffected by infusion of captopril i.a. in normal rabbits. In animals treated with furosemide, the ratio was increased by captopril infusion. However, the ratio change occurred in the infused and noninfused kidneys, negating a selective intrarenal effect. In the second part of this investigation the influence of a maximally effective i.a. dose of captopril was determined on intrarenal CE and RBF. The dose of 6.4 micrograms/kg/min of captopril increased LRBF slightly, but decreased the RBF response to ANG I i.a. only by 30%. Induction of a secondary pathway of intrarenal conversion of ANG I to ANG II is suggested by the latter results.

Angiotensin I↗
PubMed1986

Vascular reactivity of contralateral kidney in awake Goldblatt hypertensive dog.

Sixteen dogs were instrumented for recording mean arterial blood pressure (MAP) and blood flow from the left renal artery (RBF) and for intra-arterial infusions of norepinephrine (NE) and angiotensin II (ANG II). Nine dogs (group 1) were studied while normotensive and also when hypertensive. Seven control dogs (group 2) were studied only when normotensive. In a control session conducted in group 1 and at weekly intervals for up to 6-12 wk after the right renal artery was clipped, infusions of NE and ANG II were given intra-arterially to produce graded decreases in RBF. Group 2 was studied similarly in a control session and 4-7 wk later. Regressions of the values of percent change RBF (arc sin transformation) on the concentrations of NE and ANG II in renal arterial blood estimated the renal vascular reactivity of the hypertensives' contralateral kidney and the normotensives' kidney. In group 1, during the postclipping intervals when MAP and plasma renin activity were increased, the renal vascular reactivity to NE, but not to ANG II was increased. This was based on the significant elevation above the X axis in the postclipping regressions. In group 2, MAP, plasma renin activity, and renal vascular reactivity to NE and ANG II were unchanged over the 4- to 7-wk interval of study. These results indicate that the contralateral kidney develops an increased vascular reactivity to NE but not to ANG II in Goldblatt hypertension.

Angiotensin III↗
PubMed1986

Analysis of adrenoceptor blockade and hypotension elicited by urapidil and prazosin in conscious rat.

The adrenoceptor blocking properties and hypotensive effects of the alpha-1 blocking agents urapidil and prazosin were compared in conscious instrumented rats. Both urapidil and prazosin in i.v. doses of 3 and 6 mg/kg and 0.125 and 0.25 mg/kg, respectively, blocked the pressor response to the alpha-1 adrenoceptor agonist phenylephrine. The hypotensive effects of urapidil and prazosin in these doses were equivalent. Mechanisms of the blood pressure compensation to urapidil-induced hypotension were examined with the arginine vasopressin (AVP) antagonist, d(CH2)5Tyr(Me)AVP, and the angiotensin converting enzyme inhibitor, MK-422. Urapidil alone (6 mg/kg i.v.) and after the AVP antagonist caused a similar degree of hypotension (22 and 15% decrease, respectively, in mean blood pressure). When the alpha-1 antagonist was administered after converting enzyme inhibition, it caused a significantly greater decrease in blood pressure (37%) than in the previous two groups, but not different from that obtained after combined AVP antagonism and converting enzyme inhibition (30% decrease). These results indicate that the renin-angiotensin system compensates for the hypotensive effect due to alpha-1 adrenoceptor blockade, whereas AVP, even assuming that the circulating level was increased by urapidil, was without effect on blood pressure.

Adrenergic alpha-Antagonists↗
PubMed1985

Long-term renal and systemic effects of calcium entry blockers in normotensive and experimental hypertensive dogs.

The effect of diltiazem administered as a sustained infusion (10 to 15 micrograms/kg/min) was studied in 3 groups of conscious instrumented dogs: 4 normotensive, 5 Goldblatt hypertensive (GH) and 4 deoxycorticosterone acetate salt treated Goldblatt hypertensive (DSGH) dogs. Mean arterial blood pressure, left renal blood flow and heart rate were monitored, and the plasma renin activity was determined in a control session and after 3 to 5 days of diltiazem infusion in the normotensive and after 5 to 8 days of infusion in the 2 hypertensive groups. Pressor and renal blood flow responses to phenylephrine, norepinephrine and angiotensin II were also determined in the control session and on the last day of the diltiazem infusion. Mean arterial blood pressure was found to be decreased at the 5 to 8-day interval in the DSGHs and in the GHs, but the change in the latter group was not statistically significant. Mean arterial blood pressure was unchanged in the normotensives. Renal vascular resistance was decreased by diltiazem in the normotensive group at 3 to 5 days and in the DSGHs at 1 to 2 days. Heart rate was not significantly affected by diltiazem in the hypertensive groups, but was increased in the normotensive group at the 1 to 2-day interval. Plasma renin activity tended to increase in the hypertensive, but not in the normotensive dogs. Pressor and renal blood flow responses to all the agonist agents tested were decreased in the presence of diltiazem.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗