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Biomedical subjects

N Parekh

Publications and source records attributed to N Parekh.

At least 37 records · Page 2Linked to original sources
PubMed1996

Role of prostaglandins in renal medullary circulation: response to different vasoconstrictors.

This study investigated effects of renal prostaglandins and their interaction with different vasoactive agents in regulating regional renal blood flow. Using intravenous infusions, we compared effects of different pressor hormones and a nitric oxide (NO) inhibitor under control conditions and after inhibition of cyclooxygenase. Because vasodilator effects of prostanoids are considered to be mediated via opening of ATP-dependent K+ channels, we also studied effects of a prostacyclin analogue (iloprost), a channel opener (lemakalim), and a channel blocker (glibenclamide). Blood flow in renal cortex (CBF) and medulla (MBF) was determined with previously described platinum electrodes inserted into the kidney of anesthetized rats. Angiotensin II and norepinephrine reduced predominantly only CBF (-24 and -19%, respectively). After indomethacin, which selectively reduced MBF (-25%), angiotensin II and norepinephrine also reduced MBF (-45 and -35%, respectively), whereas the corresponding changes in CBF were not affected by indomethacin. Arginine vasopressin and the NO inhibitor NG-nitro-L-arginine methyl ester reduced both CBF and MBF by approximately 30% both under control conditions and after indomethacin. Iloprost and lemakalim increased selectively MBF (15 and 27%, respectively), whereas glibenclamide selectively decreased MBF (-19%). Our data indicate that renal prostaglandins are predominantly involved in regulating medullary circulation. They probably exert their dilatory action on medullary vessels via opening of ATP-dependent K+ channels and are involved in antagonizing medullary effects of pressor hormones in an agonist-specific manner.

Angiotensin II↗
PubMed1995

Mammographic features and breast cancer risk: effects with time, age, and menopause status.

BACKGROUND: Mammographic images from women with a high proportion of epithelial and stromal breast tissues are described as showing high-density parenchymal patterns. Most past studies that noted an increase in breast cancer risk associated with mammographic parenchymal patterns showing high density either 1) lacked information on other breast cancer risk factors, 2) were too small, or 3) included insufficient follow-up time to adequately resolve persisting doubts whether mammographic features are "independent" measures of breast cancer risk and not a detection artifact. PURPOSE: The purpose of this study was twofold: 1) to evaluate the associations between mammographic features and other breast cancer risk factors and 2) to assess effects of mammographic features on breast cancer risk by time, age, and menopause status. METHODS: To address these questions, we analyzed detailed information from a large, nested case-control study with 16 years of follow-up. This study used information from both screening and follow-up phases of the Breast Cancer Detection Demonstration Project, a nationwide program that offered annual breast cancer screening for more than 280,000 women from 1973 to 1980. Mammographic features were assessed from the base-line screening mammographic examination for 1880 incident case subjects and 2152 control subjects. Control subjects were randomly selected from women of the same age and race as each case subject. Control subjects attended the same screening center as the case subject and were free of breast cancer at the case subject's date of diagnosis. Odds ratios (ORs) with 95% confidence intervals (CIs) provided estimates of the relative risk of breast cancer. RESULTS: Mammographic features were associated with known breast cancer risk factors. However, the high-density parenchymal pattern effects were independent of family history, age at first birth, alcohol consumption, and benign breast disease. The increase risk for women with Wolfe's two high-density parenchymal patterns, P2 (OR = 3.2; 95% CI = 2.5-4.0) and Dy (OR = 2.9; 95% CI = 2.2-3.9), was explained primarily by measured percent of the breast with dense mammographic appearance. Compared with women with no visible breast density, women who had a breast density of 75% or greater had an almost fivefold increased risk of breast cancer (95% CI = 3.6-7.1). These effects persisted for 10 or more years and were noted for both premenopausal and postmenopausal women of all ages. CONCLUSIONS: Of the breast cancer risk factors assessed in the participants, high-density mammographic parenchymal patterns, as measured by the proportion of breast area composed of epithelial and stromal tissue, had the greatest impact on breast cancer risk. Of the breast cancers in this study, 28% were attributable to having 50% or greater breast density.

Age Factors↗
PubMed1995

Preservation of myocardial blood flow by calcium antagonists does not prevent attenuation of regional myocardial function after repetitive brief periods of myocardial ischaemia in the rat heart.

The aim of this study was to assess the effect of two different calcium channel blockers on myocardial blood flow and function in a rat model of myocardial 'stunning' by repeated short episodes of ischaemia ('repetitive ischaemia'). In an open chest rat model, the left anterior descending coronary artery was ligated for 10 min followed by 15 min reperfusion. In total, five periods of ischaemia and reperfusion were performed. Myocardial blood flow was assessed by the hydrogen clearance technique and systolic thickening fraction by pulsed Doppler. After five episodes of ischaemia, myocardial blood flow adn myocardial thickening in the ischaemic area were reduced by 60 +/- 8% and 52 +/- 7% (n=9), respectively, as compared to baseline. Continuous intravenous infusion of the calcium channel blockers nifedipine (n=6) and gallopamil (n=6), started 20 min prior to onset of ischaemia, attenuated the ischaemia-induced decrease of myocardial perfusion. Nifedipine was the most effective with only 5 +/- 2% reduction in blood flow after five ischaemic episodes, whereas reduction of myocardial blood flow was 30 +/- 4% in the presence of gallopamil. However, neither nifedipine nor gallopamil were able to prevent regional ventricular dysfunction induced by repetitive ischaemia. Despite the preservation of myocardial blood flow following repetitive ischaemia, calcium channel blockers do not prevent ischaemia-induced reduction of myocardial function in the ischaemic area.

Animals↗
PubMed1995

A novel method for infusing drugs continuously into the renal artery of rats.

A method is described to achieve a homogeneous intravascular distribution of drugs infused into the renal artery of anesthetized rats. The device for intrarenal infusion consisted of a multiple-catheter system with a cannula inserted into the renal artery, which was connected to different lines for drug infusions and to one line for oscillating blood back and forth in the renal cannula with a magnetic membrane pump. The blood oscillation served to mix the drugs with renal arterial blood. To verify the usefulness of this procedure, Lissamine green was infused into the renal artery; without the mixing pump the dye was located on a small portion of the kidney surface, whereas the dye could be visualized evenly distributed and less concentrated over the entire kidney with the pump. With the mixing device, intrarenal infusion of angiotensin II, 5 pmol.kg-1.min-1, or norepinephrine, 150 pmol.kg-1.min-1, reduced renal blood flow by approximately 25% without affecting blood pressure. Tenfold higher doses given intravenously had comparable renal effects, but these increased systemic pressure. Without the mixing pump, vasoactive drugs given into the renal artery had a distinctly smaller effect on renal blood flow than with the pump (angiotensin II, 39%; norepinephrine, 49%; and acetylcholine, at 5 nmol.kg-1.min-1, 33%). The results show that intrarenally infused drugs, without a mixing device, have access to an unpredictably small kidney volume, and estimation of their effects on kidney functions can be equivocal. The present device ensures an adequate mixing of drugs with renal blood.

Angiotensin II↗
PubMed1993

Sex differences in control of renal outer medullary circulation in rats: role of prostaglandins.

A calibration technique was developed to quantify blood flow changes in the renal cortex and outer medulla in rats using platinum needle electrodes sensing partial pressure of locally generated hydrogen. Measurements were made in male and female rats to investigate sex differences in the humoral control and autoregulation of regional renal circulations. In males, both cortical and outer medullary blood flows were efficiently auto-regulated above an arterial pressure of 100 mmHg. The converting-enzyme inhibitor quinapril increased blood flow by 20% in both kidney zones, and inhibition of prostaglandin synthesis by indomethacin did not change the flow. In females, similar results were obtained only for the cortex; the medulla had a different response pattern. The blood flow was not autoregulated in the experimental pressure range up to 120 mmHg; quinapril did not change the flow, but indomethacin decreased the flow by 16% and at the same time restored its autoregulation capacity. We conclude that: 1) the medulla of female rats has a high basal level of vasodilator prostaglandins, which interferes with blood flow autoregulation in this kidney area, and 2) medullary flow in female rats is little affected by endogenous angiotensin.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Activation of neutrophils in the microvasculature of the ischaemic and reperfused myocardium.

In 11 rats, the microcirculation of the repeatedly ischaemic (stunned) left ventricular myocardium was studied using in vivo fluorescence microscopy. Stunning was provoked by six subsequent 10 min ligations of the left anterior descending coronary artery, each of them followed by a 20 min reperfusion period. In the stunned myocardium showing hypokinetic wall motion, myocardial blood flow dropped by 55%; in this region, leukocytes often appeared in slow-flow capillaries plugging capillary branches. Closely linking to leukocyte adherence, a rise of microvascular permeability was documented by extravascular clouds of fluorescent dextran. After nifedipine treatment, in ischaemic regions marked dilatation of larger A1 and A2 arterioles was noted, in addition to the ischaemia-induced dilatation of smaller A3 and A4 arterioles. Furthermore nifedipine and nisoldipine reduced the number of adherent leukocytes in post-capillary venules and capillaries of the repeatedly ischaemic myocardium. In 12 patients with coronary one-vessel disease and without previous transmural myocardial infarction, elective coronary angioplasty (PTCA) was performed (balloon inflation for 2 min). After elective PTCA of the LAD, a significant rise in the proportion of activated neutrophils was noted. After elective 2 min PTCA of the LAD, coronary sinus blood samples showed a marked rise of FMLC stimulated superoxide anion production, whereas passive deformability decreased considerably. Furthermore, an increase in chemotactic activity in coronary sinus blood samples was observed.

Angioplasty, Balloon, Coronary↗
PubMed1991

Tissue PH2 measurement for continuous estimation of blood flow changes in rat kidney cortex and medulla.

A method is described for estimation of local blood flow changes in the renal cortex and medulla, based on continuous polarographic measurement of tissue pressure of electrochemically generated hydrogen (PH2). The technique was used in anaesthetized female Wistar rats. The changes in cortical PH2 were negatively correlated with those in flow velocity in the renal artery (Doppler probe). To evaluate the method, PH2 responses to a reduction of renal perfusion pressure (RPP) and to angiotensin II were examined. RPP reduction from 130 mmHg to 104 mmHg increased the cortical PH2 by 3.5% and medullary PH2 by 6.9% (difference significant at P less than 0.02). With RPP reduction from 113 mmHg to 76 mmHg the values were 6.9% and 11% respectively (difference significant at P less than 0.001). Angiotensin II infusion increased cortical PH2 by 8.7% and medullary PH2 by 4.1% (difference significant at P less than 0.005). It is concluded that the method enables continuous estimation of blood flow changes in the renal cortex and medulla.

Angiotensin II↗
PubMed1991

[Dopaminergic effect of anisodamine on the microcirculation of the hydronephrotic kidney of rats].

Anisodamine is an alkaloid extracted from the Tibetan plant "Anisodus tanguticus". Since 1965 it has been used in China for the treatment of shock but the mechanisms of its action are not fully known. The present study was performed to determine the effect of anisodamine on the renal microcirculation and to examine the underlying mechanism of its actions. The addition of anisodamine (10(-8) M to 10(-3) M) to the kidney bath resulted in a significant and dose dependent dilation of all preglomerular vessels. The maximal dilation (about 30% dilation) was found in the proximal interlobular artery. In contrast to preglomerular vessels anisodamine caused constriction of postglomerular vessels. The glomerular blood flow increased by about 50% at anisodamine concentration of 10(-3) M. Haloperidol, a dopamine receptor antagonist could abolish the renal vascular effect of anisodamine. It is suggested that anisodamine could improve renal function by the dilation of preglomerular vessels in combination with the constriction of postglomerular vessels, and the effect of anisodamine may be mediated by activation of the dopaminergic system.

Animals↗
PubMed1991

Interaction between adenosine and angiotensin II in renal microcirculation.

In order to examine the possibility of an interaction between adenosine and angiotensin II (A II) in the control of the renal microcirculation, we studied the effects of agonists and antagonists of both substances by means of in vivo microscopy in the split hydronephrotic rat kidney. In a first series of experiments (n = 6), local application of the A II receptor antagonist saralasin (10(-6) mol.liter-1 abolished the vasoconstriction and the reduction of glomerular blood flow induced by the A1-adenosine receptor agonist N6-cyclohexyladenosine (CHA, local concentration 10(-7) mol.liter-1). Without saralasin (second series, n = 6), CHA reduced glomerular blood flow and decreased vessel diameters as previously reported from our laboratory. In a third series of experiments (n = 6), A II significantly reduced vessel diameters and glomerular blood flow both alone and during blockage of the A1-adenosine receptor by the selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10(-5) mol.liter-1). In additional experiments, we excluded nonspecific receptor effects of saralasin and confirmed the inhibitory action of DPCPX on the adenosine-induced vasoconstriction. We suppose that adenosine needs a functioning A II receptor system for its vasoconstrictor action, whereas A II can induce a nonadenosine-dependent vasoconstriction.

Adenosine↗
PubMed1991

Cysteinyl leukotriene actions on the microcirculation of the normal and split hydronephrotic rat kidney.

The effects of leukotriene D4 (LTD4) and leukotriene E4 (LTE4) on renal microcirculation were determined on normal and hydronephrotic female Wistar rats. In normal kidneys, the effects of LTD4 on total renal blood flow and glomerular filtration rate were measured by a flow meter and by inulin clearance. In the split hydronephrotic kidney, the LTD4- and LTE4-mediated vascular effects were localized by intravital microscopy. Intravenous infusion of low-dose LTD4 (1 x 10(-9) mol min-1 kg-1) over 15 min induced a strong decrease in renal blood flow (-43% and -70%) in the normal and the hydronephrotic kidney. After the infusion the glomerular filtration rate of the normal kidney was significantly reduced by 65% and the filtration fraction by 32%. The fall in filtration fraction is in accordance with the significant decrease in luminal diameters of the arcuate artery (-28%) and the proximal interlobular artery (-12%) in the hydronephrotic kidney under LTD4. The decrease in renal blood flow, glomerular filtration rate, filtration fraction and luminal diameters persisted in the normal as well as in the hydronephrotic kidney for more than 60 min beyond cessation of infusion. Local application of LTD4 (1 x 10(-10) mol l-1 up to 1 x 10(-7) mol l-1) and LTE4 (1 x 10(-10) mol l-1 up to 1 x 10(-8) mol l-1) induced a dose-dependent constriction of the arcuate artery and the proximal interlobular artery. The distal interlobular artery, the afferent and the efferent arteriole were not significantly affected by LTD4 or LTE4. The glomerular blood flow was dose-dependently reduced up to 48% under local LTD4 and 43% under LTE4. The LTD4/LTE4 antagonist FPL 55712 (1 x 10(-8) mol min-1 kg-1, iv) significantly attenuated the effects of LTD4 infusion and local LTE4 application in the hydronephrotic kidney. This is indicative of the presence of receptors for LTD4 and LTE4 in the larger preglomerular vessels of the rat kidney. The LTD4 effects on the normal kidney were attenuated by simultaneous infusion of dopamine (5 microgram min-1 kg-1) or plasma expansion, two principal methods in the treatment of acute renal failure. The results in the normal and hydronephrotic kidney demonstrate a preferential preglomerular vasoconstriction under LTD4 and LTE4 causing a marked decrease in renal and glomerular blood flow, glomerular filtration rate and filtration fraction.

Animals↗
PubMed1991

Calcium antagonists and myocardial microperfusion.

Recent studies have improved our understanding of the beneficial actions of calcium antagonists on myocardial microcirculation and metabolism. The effect of calcium antagonists on the microcirculation of the left ventricular rat myocardium was studied using in vivo microscopic techniques. Intravenous verapamil 0.3 mg/kg and nifedipine 75 micrograms/kg produced a 15 to 18% increase in the diameter of larger A1 and A2 coronary arterioles (range 31 to 300 microns); diameters of terminal (A4) arterioles and capillaries did not change significantly. Furthermore, verapamil significantly (p less than 0.001) increased the ratio of capillaries filled with red cells to those containing plasma alone. Verapamil pretreatment produced a similarly selective dilatation of larger coronary arterioles and protected against the ischaemia-induced fall in capillary red cell content. Spectroscopic data show that verapamil also produces an increase in myocardial phosphocreatine and preservation of adenosine triphosphate (ATP) during ischaemia in the Langendorff-perfused heart. In patients with exercise-induced angina, gallopamil decreased global myocardial 201Tl and 123I phenylpentadecanoic acid (IPPA) uptake due to a reduction in myocardial oxygen consumption. Regional 201Tl and IPPA uptake as well as IPPA clearance in post-stenotic areas tended to rise after gallopamil treatment. Thus, the beneficial effects of calcium antagonists such as verapamil or gallopamil in patients with ischaemic heart disease may result from dilatation of predominantly larger arterioles. Consequently, there is an improvement in regional perfusion and free fatty acid utilisation in reversibly ischaemic regions.

Animals↗
PubMed1990

A narrow segment of the efferent arteriole controls efferent resistance in the hydronephrotic rat kidney.

We microscopically examined the narrow segment of the efferent arteriole (NSEA) in the hydronephrotic kidney of rats in vivo. This segment is routinely found at the proximal efferent arteriole adjacent to the glomerulus and is characterized by a narrowing due to a cellular structure which bulges into the lumen. The existence of NSEA has been described in a previous study from our laboratory, but it was not examined in detail; its functional behavior in particular is still unknown. In the present study, we measured changes in luminal diameter of NSEA during reduction of renal perfusion pressure and in response to angiotensin II (Ang II), saralasin, and nitroprusside. The mean luminal diameter of NSEA at its narrowest point was 5.1 microns and its effective length was 8.4 microns. Reduction of renal perfusion pressure from 115 to 90, 70, and 40 mm Hg decreased NSEA diameter by 9, 15, and 23%, respectively. Topical application of saralasin (10(-5) M) or nitroprusside (10(-4) M) to the kidney dilated NSEA by 10 or 20%, respectively, and attenuated the pressure-dependent constriction of NSEA. Intravenous infusion of Ang II at rates of 50, 100, 200, and 400 ng/min/kg constricted NSEA lumen by 7, 15, 20, and 21%, respectively. The vascular bed of the hydronephrotic kidney was scanned morphologically, and a mathematical model was developed from these data. With this model, we could calculate the effect of segmental diameter changes on total renal resistance as well as flow and pressure at different vascular levels. NSEA contributed 4% to the total renal resistance and 20% to the efferent resistance under control conditions. Lowering of renal perfusion pressure increased the efferent arteriolar resistance up to 50% above the control value mainly as a result of constriction of NSEA. Our data indicate that efferent resistance increases at reduced renal perfusion pressure and leads to a stabilization of glomerular pressure. The rise of efferent resistance is mediated primarily by NSEA constriction, and the renin-angiotensin system is involved in this regulation.

Angiotensin II↗
PubMed1990

Sex differences in autoregulation of juxtamedullary glomerular blood flow in hydronephrotic rats.

The technique of the split hydronephrotic kidney of anesthetized Wistar rats was used for the first time to study afferent and efferent arterioles of juxtamedullary (JM) glomeruli in vivo and to compare their behavior with that of the cortical glomeruli in female (F, 270 g body wt) and male (M, 400 g body wt) rats. The mean length of cortical efferent arterioles (F, 260; M, 380 microns) was less than 10% the length of JM efferent arterioles. Luminal diameters of the JM afferent arteriole (F, 17.1; M, 18.3 microns) and efferent arteriole (F, 25; M, 33.4 microns) were much larger than those of cortical arterioles (afferent: F, 9.1, M, 10.5 microns; efferent: F and M, 11.1 microns). In the hydronephrotic kidney, cortical glomerular blood flow (F, 17.5; M, 18.3 nl/min) is much reduced compared with the normal filtering kidney. This, however, is not true of JM glomerular blood flow (F, 120; M, 262 nl/min). During the reduction of renal perfusion pressure in females blood flow was autoregulated in cortical glomeruli within the pressure range of 110 to 80 mmHg; JM glomeruli failed to show any autoregulation. In males the glomerular blood flow was similarly autoregulated down to 90 mmHg in both cortical and JM nephrons. Local application of indomethacin to the kidneys from female rats reduced the glomerular flow rates by 30% but changed the autoregulatory behavior of cortical and JM glomerular blood flow so that it resembled that observed in untreated males. The data suggest that in females the autoregulatory response, particularly in JM glomeruli, is modified by prostaglandins.

Animals↗
PubMed1990

Pharmacokinetics of technetium-99m-MAG3 in humans.

Technetium-99m-mercaptoacetylglycylglycylglycine (99mTc-MAG3) is introduced to replace o-iodohippurate (OIH) for renal function studies. For interpretation of clinical findings, extensive pharmacokinetic studies were performed on patients. These showed that 99mTc-MAG3, compared with OIH, has a higher plasma-protein binding, an essentially higher intravascular concentration, a smaller volume of distribution and, with practically identical biologic half-lives, a correspondingly lower clearance. Simultaneous steady-state measurements resulted in a 1.5-fold higher clearance of OIH than of 99mTc-MAG3 (n = 124). Competitive inhibition of the tubular transport system by p-aminohippurate (PAH) (20 patients) revealed a distinctly higher suppression of the 99mTc-MAG3 clearance than of OIH which indicates a lower affinity of the 99mTc complex to the tubular cell. The plasma extraction efficiencies of both agents, measured during surgery (n = 5), did not indicate an extrarenal elimination of 99mTc-MAG3. This new radiopharmaceutical is a pragmatic alternative to OIH and offers advantages not only for scintigraphic imaging but is also suited for quantitative renal function studies.

Humans↗
PubMed1990

Microcirculation in the hypertrophic and ischemic heart.

1. Myocardial hypertrophy, for instance in patients with hypertensive heart disease, is characterized by a reduction of coronary vascular reserve, even in the presence of normal coronary arteries. In hypertensive animals, on the microcirculatory level functional changes can be observed before the onset of any structural rarefications. In 10 rats with renal hypertension and pressure-induced left ventricular hypertrophy (LVH), the microcirculation of the left ventricular myocardium was studied using in vivo fluorescence microscopy and morphometric analysis. Renal hypertension was provoked by clipping of the left renal artery. After 8 weeks, systolic blood pressure in LVH rats averaged 172 +/- 8 mm Hg, compared to 91 +/- 2 mm Hg in 10 normotensive (NT) rats. In LVH rats, distances of plasma-perfused capillaries were significantly increased (NT = 17.7; LVH = 20 microns; p less than 0.001). Volume density, surface density, and length density of capillaries in LVH rats were reduced by 20% compared to NT rats. Capillary red cell content as measured by the ratio of capillaries filled with red cells to those containing plasma alone (Q) in LVH animals exceeded that in NT rats (LVH: Q = 0.83 +/- 0.04; NT: Q = 0.77 +/- 0.04; p less than 0.025). During hypoxia (H, 5% O2) capillary red cell recruitment in LVH rats (Q: control c = 0.83; H = 0.95) was diminished by 33% as compared to NT rats (Q: c = 0.77; H = 0.95). Thus, in addition to the decreased capillary density, the reduction of capillary red cell recruitment may be responsible for chest pain in patients with LVH and normal coronary arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗