Effects of papaverine and hemorrhage on renin secretion in the nonfiltering kidney.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
R L Prewitt
Publications and source records attributed to R L Prewitt.
In vivo morphometric analysis of muscle microcirculation in dystrophic mice.
In order to test the vascular hypothesis of muscular dystrophy, the gracilis muscle in 6- to 7-week-old C57BL/6J-dy2J normal and dystrophic mice was studied using in vivo quantitative morphometric techniques to determine the total length and surface area of capillaries in which blood was flowing per unit volume of muscle. Individual capillary lengths, diameters, and red blood cell velocities were also quantified. During resting conditions, the capillary density(length per unit volume of muscle) and surface area are increased significantly in dystrophic muscle compared to normal muscle. Under fully vasodilated conditions, the capillary density and surface area are similar in normal and dystrophic muscle. Individual capillary lengths, diameters, and red blood cell velocities are also similar in normal and dystrophic muscle under resting conditions. These results indicate that, contrary to the vascular hypothesis, dystrophic muscle at rest has increased capillary density, surface area, and blood flow. It is postulated that the increased capillary density in dystrophic muscle at rest is secondary to muscle fiber breakdown.
Animals↗
Impaired arteriolar mechanotransduction in experimental diabetes mellitus.
Decreased arteriolar distensibility in diabetes may impair signal transduction mechanisms that are required for converting a pressure stimulus into smooth muscle contraction. These studies aimed to determine if pressure-induced increases in arteriolar intracellular Ca(2+) are altered in diabetes and whether diabetes is associated with alterations in composition of the extracellular matrix. Studies of mechanical properties used single, isolated, and cannulated cremaster arterioles from streptozotocin (60 mg/kg) diabetic rats and age-matched controls. To measure Ca(2+)(i), arterioles were loaded with Fura 2 (5 microM) after which preparations were examined by fluorescence microscopy and image analysis. Matrix protein (type IV collagen, laminin, fibronectin) deposition was studied by immunohistochemistry. Over a range of 30-120 mm Hg control vessels showed a linear relationship (r = 0.98, p < 0.01) between intraluminal pressure and Ca(2+)(i). Vessels from diabetic animals also showed a linear relationship (r = 0.99, p < 0.01), however, the mean slope was significantly (p < 0.02) less in the diabetic (0.17 +/- 0.05, n = 5) compared to controls (0.51 +/- 0.09, n = 7). Similarly, the slope of the wall tension-Ca(2+)(i) relationship was significantly decreased in vessels from diabetic animals. These differences were ameliorated by treatment of diabetic animals (n = 5) with aminoguanidine. Increased content of type IV collagen, laminin and fibronectin in vessel media was evident after 2 weeks of diabetes and showed a further increase with duration of diabetes. The data suggest that for a given increase in luminal pressure arterioles from diabetic animals response with an attenuated rise in smooth muscle Ca(2+)(i). This mechanotransduction defect may relate to alterations in the composition of the extracellular matrix within the arteriolar wall.
Animals↗
Feline hypoxic pulmonary vasoconstriction is not blocked by the angiotensin I-converting enzyme inhibitor, captopril.
Because of evidence that angiotensin II may be necessary for pulmonary hypoxic vasoconstriction, we investigated the response to 3% oxygen breathing before and after the blockade of angiotensin I-converting enzyme with captopril. The left lungs of 6 cats were pump-perfused through the left pulmonary artery with blood withdrawn from the inferior vena cava. The animals were ventilated mechanically, and blood gases and pH were measured and maintained within normal limits. The pulmonary vascular resistance was calculated from measurements of pulmonary arterial pressure, left atrial pressure, and blood flow. Changes in pulmonary vascular resistance caused by 3% oxygen breathing, prostaglandin F2 alpha, angiotensin I, and angiotensin II were measured before and after captopril (20 mg/kg, i.v.). The pulmonary vascular response to hypoxia was not altered by the blockade of angiotensin II production. The responses to prostaglandin F2 alpha, and angiotensin II were unchanged as well, indicating that the vasoactivity of the pulmonary vessels was not altered. The response to angiotensin I was eliminated completely. These results indicate that angiotensin II is not necessary for, and does not alter, hypoxic pulmonary vasoconstriction in the cat.
Angiotensin-Converting Enzyme Inhibitors↗
Medial and endothelial platelet-derived growth factor A chain expression is regulated by in vivo exposure to elevated flow.
Previous work from this laboratory demonstrated that in vivo exposure to elevated arterial flow stimulates endothelial and smooth muscle cell hyperplasia concomitant with lumen enlargement, medial wall hypertrophy, and increases in medial extracellular connective tissue in rat mesenteric small arteries. In an effort to elucidate the role of growth factors in mediating this arterial remodeling response, in situ hybridization was performed on control and high flow arterial sections using 35S-labeled riboprobes for PDGF-A, PDGF-B, basic FGF, and TGFbeta1 mRNA. Results demonstrate that after exposure to elevated arterial flow for 24 h, expression of PDGF-A mRNA in the media was significantly elevated over basal levels (+215%, p < 0.001). This expression decreased towards control levels by 3 and 7 days. Increased endothelial expression of PDGF-A mRNA over basal levels was evident after 3 and 7 days of elevated flow (+129%, p < 0.01; +182%; p < 0.01, respectively). Acute medial PDGF-A mRNA expression may result from elevated circumferential hoop stress secondary to flow-induced dilation while delayed expression in the endothelium may result from normalization of wall shear stress. Endothelial expression of PDGF-B mRNA was significantly elevated over control levels (+62%, p < 0.01) after exposure to high flow for 7 days. Expression of bFGF and TGFbeta1 mRNA was not significantly different between control and high flow vessels at all times measured. These results suggest a role for PDGF-A in regulating acute arterial remodeling following in vivo exposure to elevated flow.
Animals↗
Vascular research at INABIS 98.
Explore the source record for details and available documents.
Animals↗
Antihypertensive polar renomedullary lipid, a semisynthetic vasodilator.
Explore the source record for details and available documents.
Animals↗
Alkyl ether analogs of phosphatidylcholine are orally active in hypertensive rabbits.
1-0-alkyl ethers of phosphatidylcholine having an acetoyl in the second position were derived from fresh renal tissue. The main ether so derived had a 16:0 chain. The C16:0 alkyl ether was synthesized de novo. The renally derived and the synthetic ether exerted a similar and powerful antihypertensive action in hypertensive rabbits when given orally in divided doses. This action was prolonged, requiring more than 60 hours after the last input of the compound for recovery of the arterial pressure. As these ethers exerted their antihypertensive action, there was no evidence of adverse effects. Noteworthy was the failure of these depressor compounds to cause renin release. Diuresis-kaliuresis did not occur. A suggestion of sodium retention was noted.
Administration, Oral↗
Analogs of phosphatidylcholine: alpha-adrenergic antagonists from the renal medulla.
Antihypertensive polar renomedullary lipid (APRL), a conglomerate of 1-0-alkyl-2-acetoyl-glycero-3-phosphocholine analogs, ws tested in 4- to 6-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats using microcirculatory techniques. APRL (0.5 ug/ml), when added to the solution bathing the cremaster muscle, caused significant changes in the diameter, red blood cell velocity, and blood flow in both groups of rats, for arterioles and venules. Arteriolar changes in diameter were significantly greater (p less than 0.05) in SHR than in WKY. Micropipette application of APRL indicated a dose-dependent response for arterioles and venules in both groups. Moreover, the potent nature of this compound was demonstrated. Relative potency of APRL given intravenously was tested in 10- to 12-week-old SHR and WKY. The response curve was shifted significantly to the left for SHR (p less than 0.01). APRL interaction with known controllers of blood flow was tested in SHR. Blockade of cholinergic, beta-adrenergic, or histaminergic receptors did not inhibit APRL action. blockade of prostaglandin or bradykinin synthesis did not prevent depression of blood pressure by APRL. APRL (40 ug/kg) inhibited (p less than 0.001) the pressor response to norepinephrine (1-10 ug/kg) but not to angiotensin II (4 ug/kg). The present study provides direct evidence that APRL is a vasodilator with increased potency in SHR hypertension. The acute vascular response may be mediated by alpha-adrenergic antagonism.
Adrenergic alpha-Antagonists↗
Attenuation of the microcirculation in young patients with high-output borderline hypertension.
Previous studies have shown abnormalities of the microvasculature in the spontaneously hypertensive rat and human subjects with established hypertension. We have studied the conjunctival microvasculature in relation to systemic and forearm hemodynamics in 24 normal subjects (NL) and 10 subjects with intermittent elevation of blood pressure (BHT). Macrophotographs of the conjunctival circulation were measured for arteriolar diameter and density of arterioles, capillaries, and venules. Blood pressure was measured by Arteriosonde, cardiac index by echocardiography, and forearm hemodynamics by mercury-filled strain-gauge venous occlusion plethysmography. Average diastolic blood pressure in the NL group was 74 +/- 1.7 mm Hg, while that of the BHT subjects was 89 +/- 3.1 mm Hg (p less than 0.005). Capillary density, venous density, and total vascular density were significantly lower in the BHT than NL group, while arteriolar density did not differ significantly. Cardiac index was significantly higher, and peripheral vascular resistance significantly lower, in the BHT as compared to the NL subjects. Forearm blood flow was higher in the NL subjects. The diameter of the preterminal arterioles of the BHT subjects was 27% greater than NL (p less than 0.02). The capillary density was inversely related to the cardiac index (r = -0.482, p less than 0.01), but was not related to blood pressure (r = -0.207). We conclude that the high cardiac output phase of early essential hypertension in humans is accompanied by a reduction in the number of filtering capillaries, and that the rarefaction of capillaries is more closely related to the elevation of cardiac output than to raised blood pressure.
Adult↗