Biomedical subjects

K Cockrell

Publications and source records attributed to K Cockrell.

17 recordsLinked to original sources

PubMed2001

Effect of angiotensin II synthesis blockade on the hypertensive response to chronic reductions in uterine perfusion pressure in pregnant rats.

The purpose of this study was to examine the role of the renin-angiotensin system in mediating the hypertension in response to chronic reductions in uterine perfusion pressure (RUPP) in conscious chronically instrumented pregnant rats. Mean arterial pressure was significantly higher in pregnant rats with chronic RUPP (125+/-3.0 mm Hg, P<0.01, n=12) than in pregnant rats (100+/-2.3 mm Hg, n=17). Plasma renin activity in pregnant rats with chronic RUPP was 17.1+/-2.5 nmol angiotensin I. L(-1). h(-1) compared with 21.9+/-3.5 nmol angiotensin I. L(-1). h(-1) in pregnant rats. Chronic oral administration of a converting-enzyme inhibitor (enalapril, 250 mg/L for 6 days) decreased mean arterial pressure to a similar extent in pregnant rats with chronic RUPP (109+/-4.2 mm Hg, P<0.01, n=9) and in normal pregnant (81+/-1.8 mm Hg, P<0.01, n=9) rats. Blockade of the renin-angiotensin system, however, had no significant effect on the blood pressure response to chronic RUPP as differences were similar in control (Delta25 mm Hg) and converting-enzyme inhibitor-treated (Delta27 mm Hg) groups. These findings suggest that the renin-angiotensin system does not play a major role in mediating the hypertension produced by chronic RUPP in pregnant rats.

Angiotensin II↗

PubMed2000

Distribution of renal medullary hyaluronan in lean and obese rabbits.

BACKGROUND: Obese individuals have an expanded interstitium in the renal inner medulla (IM), which stains positively with periodic acid-Schiff and Alcian blue. In obese dogs, the IM is also expanded, with hyaluronan (HA) content being 2.4 times control. METHODS: We determined the anatomic pattern of renal HA deposition following weight gain, using an animal model of obesity consisting of young rabbits (N = 10), representing animals entering into the study, lean rabbits (N = 19), fed a control diet, and obese rabbits (N = 19), fed a high-fat diet (15% fat, by fortifying with corn oil and lard, in a ratio of 2:1) for two to three months. Tissue was papain digested, and HA was recovered in a phosphate or a Tris buffer and detected by an indirect immunoabsorbent competition assay. RESULTS: Rabbits fed a high-fat diet for 8 to 12 weeks gained weight (37%) and became mildly hypertensive (10 mm Hg). In lean rabbits, HA was low in the renal cortex (6 +/- 30 microg/g tissue), increased steadily across the outer medulla (OM; 79 +/- 28 microg/g tissue) and was uniformly high in the IM (192 +/- 28 microg/g tissue) when recovered in a Tris buffer; these levels of tissue HA did not change during the three-month period of dietary intervention. In obese rabbits, the renal medullary interstitium was expanded and stained intensely with periodic acid Schiff and Alcian blue, and tissue HA was elevated in the IM (448 +/- 25 microg/g tissue) but not the cortex (5 +/- 25 microg/g tissue) or the OM (85 +/- 25 microg/g tissue). The significant difference was due to those IM samples taken from the renal papilla; IM samples from the body of the kidney did not significantly differ among the lean, obese, and young rabbits. CONCLUSION: The elevated renal HA associated with weight gain is limited to the IM and occurs most consistently in the papilla, which is the region of the kidney that is most vulnerable to distention caused by elevated renal interstitial hydrostatic pressure.

Age Factors↗

PubMed1999

Diastolic compliance is reduced in obese rabbits.

Obesity often leads to symptoms of cardiopulmonary congestion associated with normal systolic but abnormal diastolic function. This study analyzed alterations in passive diastolic compliance in obesity using the rabbit model. New Zealand White rabbits were fed a normal (n=8) or 10% added fat diet (n=8). After 12 weeks, rabbits fed the high fat diet developed obesity (5.34+/-0.11 versus 3.68+/-0. 04 kg, P</=0.05) and left ventricular hypertrophy (1.37+/-0.07 versus 0.98+/-0.03 g dry weight, P</=0.05). Compliance was assessed with the isolated heart preparation by analyzing the passive end-diastolic left ventricular pressure-volume relationship. The pressure-volume relation was fit to an exponential function by regression analysis; results showed that the modulus of stiffness was greater in obese than in lean rabbits (1.21+/-0.16 versus 0. 83+/-0.05, P</=0.05), indicating that diastolic compliance was reduced. Computer simulation analyses suggested that an isolated reduction in diastolic compliance may contribute to elevated cardiac filling pressures and exercise intolerance. These data suggest that diastolic compliance is reduced early in the development of obesity and may be an important component in the reduction of cardiac reserve in obesity.

Animals↗

PubMed1998

Renal size and composition in hypertensive, obese rabbits.

OBJECTIVE: To determine whether the renal growth associated with obesity is due to hypertrophy or hyperplasia. DESIGN: New Zealand white female rabbits were fed either standard rabbit chow (n=17) or chow fortified with 10% corn oil plus 5% lard (n=18) for 12-16 weeks. MEASUREMENTS: All rabbits were weighed, and intra-arterial blood pressures were successfully measured at the end of the study in 16 lean and 18 obese rabbits; percent water of entire kidneys (8 lean, 8 obese rabbits) and of defined regions of kidneys (8 lean, 10 obese rabbits) were obtained gravimetrically. Renal hemoglobin, protein and DNA was measured chemically (8 lean, 8 obese rabbits). RESULTS: Kidneys grew in size as the rabbits gained fat. In a series of 8 lean and 8 age-matched obese rabbits, weighing 3.7+/-0.1 kg and 5.4+/-0.4kg (P<0.05), the kidneys were 20% larger in the obese rabbits: 15.0+/-0.9 g vs 18.0+/-2.5 g (P<0.05). Kidney protein was also 20% greater in the obese rabbit: 1.38+/-0.06 g/kidney vs 1.66+/-0.06 g/kidney (P<0.05). While total renal DNA was 16% greater in the obese: 18.2+/-0.5 microg/kidney vs 21.1+/-0.61 g/kidney (P<0.05), no significant difference existed when the DNA was expressed as microg/mg protein. Fractional water content of the intact kidney declined with obesity: 78.7+/-1.1% vs 76.0+/-1.2% (P<0.05). Conversely, the hemoglobin content of the kidney at autopsy, an estimate of the unstressed vascular volume, increased with obesity: 55+/-19 mg/kidney vs 82+/-25 mg/kidney (P<0.05). By contrast, water content of renal parenchyma was constant: 80.8+/-1.0% vs 80.9+/-1.2% (cortex); 84.0+/-0.8% vs 83.6%+/-2.0% (outer medulla); and 85.7+/-0.8% vs 86.0+/-2.1% (inner medulla). CONCLUSION: The renal growth associated with obesity was predominantly hyperplastic and was associated with a partial exclusion of fluid from the renal sinus.

Animals↗

PubMed1997

Obese hypertensive rabbits develop concentric and eccentric hypertrophy and diastolic filling abnormalities.

We have developed a new small animal model of obesity in which rabbits fed a high diet develop abnormalities in common with obese humans, including left ventricular (LV) hypertrophy. Using M-mode and two dimensional Doppler echocardiography we examined the characteristics of LV hypertrophy and diastolic function in obese and lean rabbits. Obese rabbits had greater interventricular septum and LV posterior wall thickness and greater LV internal end-diastolic and end-systolic diameters. Functionally, obese rabbits had higher A/E ratios. Similarly to obese humans, obese hypertensive rabbits developed combined concentric and eccentric LV hypertrophy and diastolic filling abnormalities. Therefore, this model may be valuable in the study of the development and pathology of obesity-related LV hypertrophy.

Animals↗

PubMed1997

Cholesterol feeding does not alter renal hemodynamic response to acetylcholine and angiotensin II in rabbits.

Aortic ring studies have demonstrated a decrease in endothelium-dependent relaxation or an enhanced response to vasoconstrictors in rabbits fed a high-cholesterol diet. Whether such abnormalities exist in the renal circulation is unclear. The purpose of this study was to determine functional renal responses to acetylcholine (ACh) or angiotensin II (ANG II) infusion in anesthetized rabbits after 8-10 wk of either a control diet (ACh, n = 6; ANG II, n = 6) or a 1% cholesterol diet (ACh, n = 7; ANG II, n = 7). Mean arterial pressure (MAP), renal blood flow (RBF), and glomerular filtration rate (GFR) were measured. Renal vascular resistance (RVR) was calculated as MAP/RBF. For ANG II experiments, captopril (15 microg x kg(-1) x min(-1)) was infused to suppress endogenous ANG II production. After two control clearance periods, either ACh (1 microg x kg(-1) x min(-1)) or ANG II (0.5 ng x kg(-1) x min(-1)) was infused into the renal artery; RBF was allowed to stabilize before experimental clearances. RBF increased with ACh (control: 25 +/- 2 to 39 +/- 2 ml/min; cholesterol: 26 +/- 2 to 40 +/- 3 ml/min) and decreased with ANG II infusions (control: 40 +/- 4 to 25 +/- 3 ml/min; cholesterol: 36 +/- 3 to 24 +/- 2 ml/min). Nitrate/nitrite excretion also increased with ACh infusion (control: 2.3 +/- 1.0 to 5.2 +/- 1.8 nmol x kg(-1) x min(-1); cholesterol: 2.3 +/- 0.3 to 6.0 +/- 1.3 nmol x kg(-1) x min(-1)). However, there were no significant differences between control and cholesterol groups in either response. GFR was unaltered during ACh and ANG II infusions. MAP, RVR, and urinary sodium and potassium excretion did not differ between groups in response to either drug. These results suggest that, despite significant hypercholesterolemia and large-vessel atherosclerosis, both nitric oxideinduced vasodilation and endothelium-dependent modulation of ANG II vasoconstriction in the renal circulation are unaffected by cholesterol feeding.

Acetylcholine↗

PubMed1997

Reduced sensitivity of the renal circulation to angiotensin II in pregnant rats.

The renal circulation undergoes significant changes during pregnancy and pregnancy-induced hypertension. Although numerous studies indicate that the pressor response to angiotensin II (Ang II) is reduced during pregnancy, it is unclear as to whether this altered sensitivity to Ang II occurs in the renal circulation. The first aim of this study was to determine whether the renal vascular responsiveness to exogenous Ang II is altered in the midterm pregnant rat. All rats were pretreated with an intravenous infusion of the converting-enzyme inhibitor captopril (20 microg x kg(-1) x min(-1)) to block endogenous Ang II formation. Following a control period, Ang II was infused at a dose of 10 ng x kg(-1) x min(-1) for 50 minutes into the renal arteries via a suprarenal aortic catheter. In anesthetized virgin rats, Ang II markedly decreased renal plasma flow (RPF) by 39% (5.0+/-0.4 to 3.1+/-0.4 mL/min), glomerular filtration rate (GFR) by 39% (1.9+/-0.1 to 1.16+/-0.2 mL/min), and urine flow by 47% (22.1+/-5.6 to 12.3+/-4.8 microL/min). In contrast, Ang II had no significant effect on RPF, GFR, and urine flow in the anesthetized pregnant rats. Since nitric oxide (NO) has been previously reported to modulate the renal vascular actions of Ang II in normal animals and NO synthesis is thought to be elevated in pregnancy, this study examined the role of NO in the attenuated renal response to Ang II. In pregnant rats pretreated with L-NAME, the arterial pressure was higher and RPF was lower than in the control pregnant rats. However, the renal response to Ang II in the L-NAME-pretreated pregnant rats was similar to control pregnant rats. These data indicate that the renal circulation has a reduced sensitivity to Ang II during pregnancy. We also found that NO synthesis inhibition does not alter the attenuated renal response to Ang II in the anesthetized pregnant rats.

Angiotensin II↗

PubMed1997

Reduced cardiac contractile responsiveness to isoproterenol in obese rabbits.

Although obesity is characterized by increased sympathetic nervous system activity, there is often a paradoxical reduction in cardiovascular end-organ response to sympathetic stimulation. Mechanisms involved in reduced sympathetic responsiveness in obesity have not been well characterized. Therefore, we determined cardiac contractile responsiveness to beta-stimulation in the obese rabbit model using both isolated heart (IH) and isolated papillary muscle (IPM) preparations. Female New Zealand White rabbits were fed control (IH: n=9; IPM: n=6) or 10% fat diets (IH: n=9; IPM: n=7) for 12 weeks. Contractile responsiveness in the IH was determined using a modified Langendorff preparation to evaluate the dose-response relationship between isoproterenol and 1) peak developed pressure/g of left ventricular wet weight and 2) maximal rate of pressure development (+dP/dt/P). Contractile responsiveness in the IPM was determined using right ventricular papillary muscles to evaluate the dose-response relationship between isoproterenol and (1) peak developed tension (T)/mm2 cross-sectional area (CSA) and (2) maximal rate of tension development (dT/dt/CSA). In the IH, baseline and maximum developed pressure/g were reduced in obese rabbits by 37% and 31%, respectively (P< or =.05). In the IPM, baseline and maximum T/CSA responses were reduced in obese rabbits by 59% and 33%, respectively (P< or =.05). Potency of isoproterenol as reflected by the EC50 did not differ between lean and obese animals in either preparation. These results demonstrate that left ventricular contractility in obesity is reduced at baseline and in response to stimulation with isoproterenol and suggest that decreased responsiveness to beta-stimulation may be a factor in the obesity-related systolic dysfunction.

Animals↗

PubMed1996

Hypertension, cardiac hypertrophy, and neurohumoral activity in a new animal model of obesity.

Although obesity is a major risk factor for morbidity and mortality, the mechanisms mediating cardiovascular abnormalities in response to weight gain are unclear. One reason for the paucity of information in this area is the lack of appropriate animal models for the study of human obesity. Therefore, the goal of the present study was to develop a small animal model of dietary-induced obesity that mimics many of the characteristics of human obesity. We studied female New Zealand White rabbits fed either a normal (n = 17) or high-fat diet (n = 15) and examined the cardiovascular consequences of obesity, including changes in blood pressure, humoral activation, and end-organ effects such as cardiac hypertrophy. After 12 wk, rabbits on the high-fat diet were 46% heavier than their lean counterparts (5.49 +/- 0.09 vs. 3.77 +/- 0.06 kg, respectively; P = 0.0001). Obese rabbits had higher resting heart rates than lean rabbits (220 +/- 7 vs. 177 +/- 6 beats/min; P = 0.0001) and developed hypertension (96 +/- 2 vs. 85 +/- 1 mmHg; P = 0.0001), hyperinsulinemia (32.5 +/- 3.4 vs. 15.5 +/- 1.0 microU/ml; P = 0.0001), hyperglycemia (162.4 +/- 2.9 vs. 141.9 +/- 2.7 mg/dl; P = 0.0001), and elevated triglycerides (102.3 +/- 9.1 vs. 48.5 +/- 4.0 mg/dl; P = 0.0001). Obese rabbits also developed cardiac hypertrophy, as evidenced by left ventricular (LV) dry weights that were 52% greater in obese than in lean rabbits (P = 0.0003). In addition, LV total protein was increased in proportion to the increase in LV weight. The results of this study suggest that rabbits fed a high-fat diet for a period of 12 wk develop many of the characteristics of human obesity. The obese rabbit should provide a small and relatively inexpensive animal model to investigate mechanisms of obesity-related cardiovascular abnormalities.

Animals↗

PubMed1995

Hemodynamic alterations in hypertensive obese rabbits.

There is little information on changes in overall and regional hemodynamics in obesity-associated hypertension. Therefore, the purpose of this study was to determine alterations in overall and regional blood flows and resistances in adipose and nonadipose tissues in a new model of obesity-associated hypertension in rabbits. Sixteen female New Zealand White rabbits were fed either a maintenance or high-fat diet; after 8 to 12 weeks cardiac output and regional blood flows were measured with the use of radioactive microspheres. Obese rabbits (5.22 +/- 0.14 versus 3.66 +/- 0.04 kg) had higher blood pressure (113 +/- 3 versus 95 +/- 1 mm Hg), cardiac output (812 +/- 59 versus 593 +/- 47 mL/min), and heart rate (269 +/- 12 versus 219 +/- 9 beats per minute) and lower overall peripheral resistance (0.14 +/- 0.01 versus 0.17 +/- 0.01 mm Hg/[mL/min]) than lean rabbits. Compared with lean controls, obese rabbits had higher weights of the ventricles, kidneys, liver, ovaries, adrenals, diaphragm, and spleen. Absolute blood flows were greater in the ventricles, kidneys, lungs, and ovaries, but differences were minimized when flows were normalized for organ weight. Adipose tissue flow per gram weight was significantly lower and resistance higher in obese rabbits. However, calculated total adipose tissue flow was higher in obese rabbits (86 versus 45 mL/min). Absolute resistances were lower in the left ventricle, kidneys, and large intestine, but when resistances were indexed for organ weight, kidney resistance tended to be higher in obese rabbits. These results indicate that even short periods of obesity-associated hypertension result in marked overall and regional hemodynamic changes.

Adipose Tissue↗

PubMed1995

Renal sinus lipomatosis and body composition in hypertensive, obese rabbits.

OBJECTIVE: To test whether renal lipomatosis, an accretion of fat in the renal sinus associated with chronic renal infections, abscesses and calculi, can also be caused by rapid weight gain. DESIGN: New Zealand white rabbits were fed either standard rabbit chow (n = 24) or chow fortified with 10% corn oil plus 5% lard (n = 25) for 8-12 weeks. MEASUREMENTS: The rabbits and constituent tissues were weighed initially, after drying and after organic extractions. Renal tissue cholesterol and triglycerides were measured chemically. RESULTS: Rabbits made obese by increased fat intake were 1.8 kg heavier than controls (5.5 +/- 0.3 kg vs 3.7 +/- 0.2; n = 24,25), had 1.54 kg more body fat (1.90 +/- 0.25 vs 0.36 +/- 0.11 kg/rabbit; n = 10,9), and had a mean arterial blood pressure that was 9.2 mm Hg greater than controls (95.1 +/- 8.5 vs 85.9 +/- 5.6 mm Hg; n = 23,24). Individual organs grew in mass (lung, 15%; gastrocnemius, 17%; liver, 27%; kidney, 30%) and their parenchyma gained extractable lipids (lung, 5.5 mg/g tissue; gastrocnemius, 9.6 mg/g tissue; liver, 17.9 mg/g tissue). Total renal triglycerides were increased 2.1 fold, from 103 +/- 36 to 219 +/- 59 mg/kidney (n = 8,8), compared to the 5.3 fold increase in whole body fat. Renal cholesterol was increased 1.7 fold, from 7.5 +/- 1.1 to 12.7 +/- 2.9 mg/kidney, (n = 8,8). Within experimental error, the sum of the total renal triglycerides plus the total renal cholesterol equaled the net fat extracted from the renal sinus alone: 95 +/- 29 mg/kidney in lean rabbits and 253 +/- 71 mg/kidney in obese (n = 17,17). CONCLUSION: Obesity alone can cause renal lipomatosis. This increased volume of anatomically localized fat may be sufficient to externally compress renal veins and lymphatics, thus altering renal hemodynamic behavior.

Animals↗

PubMed1991