Search PubMed⌕ Search

Biomedical subjects

R L Prewitt

Publications and source records attributed to R L Prewitt.

At least 37 records · Page 2Linked to original sources
PubMed1993

Alterations of mature arterioles associated with chronically reduced blood flow.

Adaptive responses of mature arterioles were examined after a 38% reduction in total blood flow to the cremaster muscle produced by unilateral orchidectomy in 12-wk-old rats. Four weeks later, the muscle was smaller than the contralateral cremaster, which did not increase in size during this period. Measured by closed-circuit television microscopy, the internal diameters of first- through fourth-order arterioles (1A-4A) were smaller, but wall cross-sectional area was reduced only in 3As. The smaller diameter of the 1A in the orchidectomy muscle resulted in unchanged wall shear rate. As determined from the perfusion-fixed, microfilled cremaster muscles, the total length of the arcading arterioles and the number of 3As were not statistically different, but the total number of 4As was significantly reduced on the orchidectomy side. Therefore, chronic load reduction in a mature muscle resulted in reduced blood flow, decreased number of 4As, and smaller arteriolar internal diameters in the absence of net changes in vascular wall cross-sectional area. A local autoregulatory mechanism related to flow-induced shear stress is suggested as the mechanism mediating the changes.

Animals↗
PubMed1992

Longitudinal effect of captopril on aortic and arteriolar development in normotensive rats.

To explore the effect of chronic converting enzyme inhibition on the macro- and microcirculation, normotensive rats were chronically given 100 mg/kg/day of captopril in their drinking water beginning one day before uninephrectomy. Cremaster arteriolar dimensions were measured 2, 4, or 8 weeks later by intravital microscopy, before and after topical application of 10(-3) M adenosine. Mean blood pressure were significantly decreased at 4 (17%) and 8 (18%) weeks in treated rats vs age-matched control. Structural diameter reductions occurred in large arterioles starting 4 weeks in treated rats, and in small arterioles at 8 weeks. The cross-sectional wall area of large arterioles increased with age in control animal, but not in captopril treated one. Eight weeks of captopril treatment also decreased the cross-sectional wall area in small arterioles. Measured by stereological techniques, small arteriolar density decreased 17% at 4 weeks and 13% at 8 weeks in treated rats. Using histological techniques, a marked reduction of medial-intimal area of the abdominal aorta was found in treated rats at 4 (24%) and 8 (15%) weeks without a significant change in internal diameter.

Animals↗
PubMed1992

Alteration of endothelial function in arterioles of renal hypertensive rats at two levels of vascular tone.

DESIGN: Arterioles were studied in vivo to determine whether the altered response to endothelium-dependent and -independent vasodilators in one-kidney, one clip (1K1C) hypertensive rats was related to increased vascular tone or precontraction with norepinephrine. METHODS: Acetylcholine, bradykinin and nitroprusside were applied topically to arterioles in the spinotrapezius muscle of 4-week 1K1C hypertensive rats and normotensive control rats. The changes in internal diameter of arcade arterioles in response to four doses of each drug were measured with intravital microscopy before and during superfusion of indomethacin. Arteriolar responses were redetermined during enhancement of vascular tone by superfusion of norepinephrine. RESULTS: Vasodilation in response to acetylcholine, but not to nitroprusside, was reduced in 1K1C rats compared with normotensive rats. Indomethacin decreased the resting arteriolar diameter, but did not alter the response to acetylcholine or nitroprusside. The response to bradykinin, which was partly attenuated after cyclo-oxygenase inhibition, was also reduced in 1K1C rats. The attenuated endothelium-dependent responses in 1K1C rats may have been a result of changes in the synthesis or release of endothelium-derived relaxing factor because the response to the endothelium-independent vasodilator nitroprusside was unchanged. Indomethacin attenuated the vasodilation of bradykinin, which suggests that prostacyclin is involved in this action in vivo. CONCLUSIONS: Precontraction with norepinephrine did not change any of the responses, indicating that the reduced endothelial-dependent responses in hypertensive rats cannot be explained by differences in vascular tone.

Acetylcholine↗
PubMed1991

Longitudinal effect of captopril on aortic and arteriolar development in normotensive rats.

Normotensive rats were chronically given 100 mg.kg-1.day-1 of captopril in their drinking water beginning 1 day before uninephrectomy. Mean blood pressure was significantly decreased 4 (17%) and 8 (18%) wk later in treated rats vs. age-matched controls. When histological techniques were used, a marked reduction of medial-intimal area of the abdominal aorta was found in treated rats at 4 (24%) and 8 (15%) wk without significant change in internal diameter. Cremaster arteriolar dimensions were measured by intravital microscopy after topical application of 10(-3) M adenosine. Structural diameter reductions occurred in large arterioles starting at 4 wk in treated rats and in small arterioles at 8 wk. Despite a significant increase in wall-to-lumen ratio of some large and small arterioles in treated rats, the wall cross-sectional area of these vessels was significantly decreased by captopril. Measured by stereological techniques, small arteriolar density decreased 17% at 4 wk and 13% at 8 wk in treated rats. Although decreased blood pressure may contribute to smaller aortic cross-sectional wall area, the effect of captopril was probably the major cause for smaller arteriolar lumens, reduced arteriolar cross-sectional wall areas, and arteriolar rarefaction.

Animals↗
PubMed1991

Microvascular development during normal growth and reduced blood flow: introduction of a new model.

The purpose of this study was to evaluate microvascular development during normal skeletal muscle maturation and to determine the alterations associated with decreased blood flow caused by a decrease in demand. Unilateral orchidectomy was performed on 4-wk-old rats to reduce muscle tension and growth of one cremaster muscle. Three weeks later, total blood flow was reduced to 58 +/- 9% measured by the dual-slit velocity technique and 55 +/- 9% by radioactive microspheres, and the muscle was smaller when compared with the intact contralateral muscle. Blood flow per gram of tissue was not significantly different. Measured by closed-circuit television microscopy, the internal diameters and wall cross-sectional areas of all orders of arterioles (1A-4A), and the number of 4As per 3A had increased with age in the control muscle. The arcading arterioles increased in length by 35% as the intact muscle grew, but the number of 3As remained unchanged. Arteriolar length increased but not in proportion to muscle mass. As a result, large and small arteriolar density decreased with age. Thus, during normal skeletal muscle maturation, preexisting arterioles became elongated and only precapillary arterioles increased in number, resulting in a decreased ratio of arteriolar number to tissue mass. Unilateral orchidectomy inhibited the growth of arterioles in both size and number. A reduced diameter of the 1A in the orchidectomy muscle resulted in unchanged wall shear rate. Flow-induced shear stress and/or local changes in growth factors are suggested as possible mechanisms mediating the alterations.

Animals↗
PubMed1991

Effect of NG-monomethyl-L-arginine on arcade arterioles of rat spinotrapezius muscles.

The effect of the specific inhibitor of nitric oxide (NO) formation NG-monomethyl-L-arginine (L-NMMA) on resting arteriolar diameter and on actions of both endothelium-dependent and -independent vasoactive substances was investigated using intravital microscopy in rats. The spinotrapezius muscle of anaesthetized normotensive rats was suspended in a Krebs-Henseleit bath containing tetrodotoxin (3 x 10(-7) M), indomethacin (2.8 x 10(-5) M), and propranolol (10(-6) M) to block sympathetic nerve conduction, prostacyclin formation, and beta-adrenergic receptors, respectively. Acetylcholine (ACh), nitroprusside (NP), norepinephrine (NE), phenylephrine (PE), and guanabenz (GB) were topically applied before and after superfusion of L-NMMA (10(-5) to 10(-4) M). Superfusion of L-NMMA reduced arteriolar diameter and caused dose-dependent increases in arteriolar tone. The onset of action of L-NMMA was nearly immediate. L-NMMA inhibited vasodilator responses to the endothelium-dependent vasodilator ACh but not to the endothelium-independent NP. NE induced dose-related vasoconstriction that was significantly potentiated by L-NMMA. These effects were partially reversed by addition of L-arginine (10(-3) M). Potentiation of vasoconstriction elicited by NE was still observed after inhibition of alpha 1-adrenoceptors with prazosin, but potentiation was abolished by the alpha 2-adrenoceptor antagonist yohimbine. L-NMMA potentiated arteriolar vasoconstriction elicited by the alpha 2-adrenergic receptor agonist GB but not by the alpha 1-adrenoceptor agonist PE. These findings with L-NMMA suggest that resting diameter of arterioles is modulated by endogenous NO biosynthesis and that endothelium-dependent vasodilators act through the formation of endogenous NO to exert their action in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effect of NG-monomethyl L-arginine on endothelium-dependent relaxation in arterioles of one-kidney, one clip hypertensive rats.

Dose-response curves to topically applied acetylcholine, bradykinin, and nitroprusside were obtained by intravital microscopy in arcading arterioles of the spinotrapezius muscle of control (n = 9) and one-kidney, one clip hypertensive (1K1C) rats (n = 11) of 4 weeks' duration before and during superfusion with the specific inhibitor of nitric oxide formation NG-monomethyl L-arginine (LNMMA) (10(-4) M) and both LNMMA (10(-4) M) and indomethacin (2.8 x 10(-5) M). Resting arteriolar tone was higher in 1K1C rats than in controls, and vasodilation to acetylcholine and bradykinin, but not to nitroprusside, was reduced (p less than 0.05) in 1K1C rats compared with controls. LNMMA increased arteriolar tone (p less than 0.05) and inhibited the vasodilator responses to acetylcholine and bradykinin (p less than 0.05) in controls but not in 1K1C rats. LNMMA did not alter the response to nitroprusside in either group. Addition of indomethacin to LNMMA increased arteriolar tone and markedly reduced the response to bradykinin, but not to acetylcholine or nitroprusside, in both groups. These findings suggest that resting arteriolar tone is increased in 1K1C rats partially because of the decreased basal release or synthesis of nitric oxide. Responses to the endothelium-dependent vasodilators acetylcholine and bradykinin were attenuated in 1K1C rats, possibly because of changes in synthesis or release of nitric oxide for acetylcholine and of prostacyclin for bradykinin, because the response to the endothelium-independent vasodilator nitroprusside did not differ between the groups.

Acetylcholine↗
PubMed1990

Captopril reduces aortic and microvascular growth in hypertensive and normotensive rats.

This experiment was designed to investigate the effect of converting enzyme inhibition on functional and structural vascular alterations in one-kidney, one clip hypertensive rats and in normotensive rats. Starting 1 day before surgery, 100 mg/kg/day captopril was given chronically to half of the hypertensive and normotensive groups in their drinking water. With use of intravital microscopy in the cremaster muscle, arteriolar dimensions were measured 4 weeks later, both before and after topical application of 10(-3) M adenosine. Mean blood pressure was 124 +/- 4 mm Hg in control rats and 103 +/- 5 mm Hg in captopril-treated control rats (p less than 0.05). Mean blood pressure was significantly elevated to 183 +/- 5 mm Hg in captopril-treated one-kidney, one clip hypertensive rats and 193 +/- 5 mm Hg in one-kidney, one clip hypertensive rats. With use of histological techniques, a marked reduction of medial-intimal area of the abdominal aorta was found in captopril-treated control rats (24%), and hypertrophy of the aortic wall in one-kidney, one clip hypertensive rats was decreased 26% by captopril. Structural diameter reductions occurred in large arterioles of the captopril-treated control and hypertensive groups and the nontreated hypertensive group. In spite of a significant increase in wall-to-lumen ratio of first-order arterioles in all captopril-treated rats, captopril decreased cross-sectional wall area of these vessels 37% in hypertensive and 20% in control rats, respectively. Measured by stereological techniques, small arteriolar density decreased 30% in captopril-treated hypertensive rats and 17% in captopril-treated control rats. Therefore, smaller arteriolar lumens, decreased aortic and arteriolar cross-sectional wall area, and arteriolar rarefaction after converting enzyme inhibition, in spite of rising or falling blood pressure, are evidence that vascular growth was inhibited in vivo.

Adenosine↗
PubMed1989

Attenuated microvascular alterations in coarctation hypertension.

Arteriolar vasoconstriction, structural reductions in dilated diameter, and rarefaction have been observed in vascular beds with chronic renal hypertension. To determine their pressure or flow dependence, these functional and structural parameters were studied in the developing and chronic stages of coarctation hypertension in the cremaster muscle, a normotensive skeletal muscle bed that is protected from the effects of elevated microvascular pressures. Hypertension was produced in rats by placing a silver clip around the abdominal aorta above the branches of the renal arteries. In hypertensive rats, resting diameters were reduced in second-order arterioles after 4 and 8 wk, in third-order arterioles after 2, 4, and 8 wk, and in fourth-order arterioles after 4 and 8 wk, vs. controls. Vascular tone was elevated in second-order arterioles after 2, 4, and 8 wk and in third- and fourth-order arterioles after 8 wk in hypertensive rats. No increases in medial-intimal area were found at any stage of hypertension in any arteriolar order. The density of small arterioles (3rd-5th orders) was reduced by 20% in hypertensive rats at 8 wk but was unchanged at the other time periods. These arteriolar alterations, especially the absence of structural reductions in diameter, are attenuated compared with those observed in one-kidney, one-clip hypertension and suggest that most of the arteriolar alterations that occur in renal hypertension are pressure or flow dependent.

Animals↗
PubMed1989

Arteriolar changes in developing and chronic stages of two-kidney, one clip hypertension.

Arteriolar internal and external diameters in the cremaster muscle of two-kidney, one clip hypertensive rats (2K1C) were measured in vivo with video microscopy, both before and after the topical application of adenosine (10(-4) M). Arteriolar density was determined by stereologic techniques. Mean arterial blood pressure was significantly elevated in the 2K1C rats, rising to 186 +/- 6 mm Hg by 8 weeks compared with 113 +/- 4 mm Hg in controls. Lumens of larger arterioles showed a structural reduction at 2 weeks of hypertension and remained at the same level through 8 weeks, while arterioles of control rats showed a progressive increase in diameter with age (101 +/- 6 microns in 2K1C vs. 158 +/- 8 microns in controls at 8 weeks after operation). Wall-to-lumen ratios of larger arterioles were significantly increased at 2, 4, and 8 weeks of hypertension, but cross-sectional wall area was significantly reduced at 8 weeks. Medial hypertrophy was not evident at any stage of hypertension. Arteriolar rarefaction of smaller arterioles was functional at 2 weeks and structural at 8 weeks of hypertension. Vascular tone of the smaller arterioles was elevated in the developing and chronic stages of hypertension. At 2 weeks of hypertension when the structural reduction in diameters of larger arterioles was progressing, the increased vasoconstriction and functional rarefaction may have contributed to the elevated resistance. At 8 weeks, the marked diameter reductions of larger arterioles (36% in first-order arterioles and 25% in second-order arterioles) account for most of the increased resistance to flow.

Abdomen↗
PubMed1989

Effects of chronic hypertension and its reversal on arteries and arterioles.

The reversibility of functional and structural microvascular alterations in chronic renal hypertension has not been established. Twelve weeks after surgery to induce hypertension, in vivo arteriolar and venular dimensions were measured in the cremaster muscle of rats with one-kidney, one-clip hypertension (1K1C), rats in which the clip was removed after 8 weeks (1KNT), and controls. Systolic blood pressure was significantly elevated after 3 days in 1K1C rats and reached a plateau by 6 weeks. In 1KNT rats, systolic blood pressures were similar to 1K1C rats but were normalized 1 day after unclipping. A marked medial-intimal hypertrophy was found by histological techniques in the thoracic and abdominal aortae (45% and 69%, respectively) but not in cremaster feeding arteries of 1K1C rats. These arterial changes were reversed after unclipping. In 1K1C rats, medial-intimal area decreased in first- through fourth-order (1A, 2A, 3A, and 4A) arterioles along with a decline in relaxed diameter (41%, 30%, 20%, and 21%, respectively), which was only partially restored after unclipping. Heart weight was increased by 67% in 1K1C rats, but it did not differ between 1KNT and controls. Therefore, the reversal of chronic renal hypertension can normalize gross structural alterations in the heart and large vessels, but more time may be required to normalize completely the arteriolar changes. These data indicate that long-term structural adaptations in renal hypertension are different in arterioles and arteries, and they may be related to chronic changes in blood flow and/or pressure.

Abdominal Muscles↗
PubMed1988

Sodium sensitivity in normotensive and borderline hypertensive humans.

The responses to sodium depletion and repletion were studied in subgroups of 92 normotensive and 65 borderline hypertensive individuals. The borderline hypertensives were characterized by significantly higher blood pressure, weight, cardiac output, hematocrit and decreased density of conjunctival capillaries and venules. Sodium-sensitivity was defined as an increase in mean arterial blood pressure exceeding 5% during sodium repletion. The prevalence of sodium-sensitivity was higher in blacks than in whites and greater in hypertensives than in normotensives. Sodium-sensitive individuals were characterized by significantly increased forearm vascular resistance and decreased plasma renin activity and aldosterone concentration. The resemblance of these changes to those reported in the Dahl salt-sensitive rat suggests a genetic basis for the response to sodium.

Aldosterone↗
PubMed1987

Alterations in the microvasculature of one-kidney, one-clip hypertensive rats.

The microcirculation was studied in the cremaster muscle of one-kidney, one-clip (1K-1C) hypertensive rats and uninephrectomized controls under chloralose-urethan anesthesia 1-2, 4-5, or 8-9 wk following renal artery stenosis. With the use of television microscopy, inside and outside diameters of first (1A) through fourth-order (4A) arterioles were measured before and after vasodilation with 10(-4) M adenosine. Mean arterial blood pressure was significantly elevated in the 1K-1C rats, rising to 170 +/- 6 mmHg by 8-9 wks vs. 93 +/- 2 mmHg in controls. Enhanced vasoconstriction, resulting in closure of arterioles, appeared only in the smaller arterioles of 1K-1C and diminished throughout the development of hypertension. Structural rarefaction appeared later and increased with the development of hypertension. Vasodilated inside diameters of control, but not 1K-1C, 1A, 2A, and 3As, increased with increasing age, leaving the hypertensive arterioles with structurally reduced lumens and increased wall-to-lumen ratios, but without increases in wall cross-sectional areas. Structural lumen reduction appeared first in the 1A and advanced downstream as hypertension developed. Thus vasoconstriction of the smallest arterioles is important initially in renal hypertension, but structural alterations become more important later.

Adenosine↗
PubMed1987

Hemodynamic characteristics of sodium-sensitive human subjects.

Fifty-eight normal subjects and 51 subjects with borderline hypertension underwent microvascular and hemodynamic studies while on an ad libitum diet and during periods of sodium depletion (10 mEq/day) and repletion (200 mEq/day). Hemodynamic measurements included arterial blood pressure, cardiac index, total peripheral resistance, forearm blood flow, vascular resistance, venous compliance, and capillary filtration fraction. Studies of the microcirculation consisted of macrophotography of the bulbar conjunctiva with measurement of anteriolar, venular, and capillary density and diameter. During sodium repletion, cardiac index increased significantly in the normal subjects (2.35 +/- 0.7 vs 2.44 +/- 0.7 L/min/m2; p less than 0.01) and in the borderline hypertensive subjects (2.50 +/- 0.7 vs 2.70 +/- 0.8 L/min/m2; p less than 0.01). However, mean blood pressure rose by more than 5% in only 33 subjects, 13 with normal and 20 with borderline hypertension. When these sodium-sensitive subjects were compared with those whose blood pressure did not rise, the former were found to have significantly higher forearm vascular resistance (32.2 +/- 21 vs 17.9 +/- 12 mm Hg/ml/min/100 g; p less than 0.01), lower forearm blood flow (4.42 +/- 2.7 vs 7.47 +/- 5.0 ml/min/100 g) and lower conjunctival capillary density (3.72 +/- 1.7 vs 5.18 +/- 2.1 [SD] mm/mm2; p less than 0.05). These results indicate that sodium sensitivity in humans is accompanied by elevation of forearm vascular resistance and attenuation of the microcirculation.

Adult↗
PubMed1987

Microvascular density changes during wound-healing.

Vessel densities of arterioles, capillaries, venules and A-V anastomoses were determined during wound-healing following implantation of the rabbit ear chamber. Arterioles were defined on the basis of the direction of blood flow and the presence of a muscular coat. Capillaries were endothelial cell tubes with single-file flow of erythrocytes. Venules were thin-walled vessels collecting blood flow from capillaries and carrying blood flow from the tissue. A-V anastomoses were thick-walled, unbranched vessels carrying blood flow from an arteriole to a venule. Arteriolar density was relatively higher in the earlier stages but venular density was higher in the later stages of wound-healing. The fractional density was highest 2 weeks after implantation for arterioles (17.9%), at 4 weeks for capillaries (39.3%), and at 10 weeks for venules (56.9%). No significant change was observed in the density of A-V anastomoses. This study suggests that the rates of growth and decay are different among each vessel category during wound-healing.

Animals↗
PubMed1986

Prevention of arteriolar rarefaction in the spontaneously hypertensive rat by exposure to simulated high altitude.

Microvascular alterations associated with reversal of hypertension by exposure to simulated high altitude were investigated in the gracilis muscle of the spontaneously hypertensive rat (SHR). Male, 4-week-old SHR were either placed in a hypobaric chamber (SHR-HA) at 430 mmHg or maintained at ambient barometric pressure (SHR-SL) for 8-10 or 12-14 weeks. Measurements of microvascular diameter and density were made by closed-circuit television microscopy. Mean arterial blood pressure was significantly lower in the SHR-HA groups. Functional arteriolar rarefaction occurred in SHR-SL at 8-10 weeks while structural arteriolar rarefaction occurred after 12-14 weeks. In contrast, neither functional nor structural rarefaction of arterioles was observed in the SHR-HA groups. Although functional rarefaction of capillaries did occur in SHR-HA, it was less than that in SHR-SL. Total capillary density, however, was similar in SHR-SL and SHR-HA after 12-14 weeks. Vasoconstriction was decreased in SHR-HA and vasodilated arteriolar diameters were greater than those of SHR-SL. These results show that simulated high altitude lowered blood pressure in SHR and resulted in a microcirculatory bed resembling that seen in a normotensive animal.

Altitude↗