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G Kaley

Publications and source records attributed to G Kaley.

At least 55 records · Page 3Linked to original sources
PubMed1997

Estrogen maintains nitric oxide synthesis in arterioles of female hypertensive rats.

We hypothesized that in female spontaneously hypertensive rats (SHR), estrogen moderates the dysfunction of arterioles by preserving nitric oxide synthesis. To this end, we conducted experiments on isolated gracilis muscle arterioles (approximately 55 microns in diameter) of 12-week-old (SHR divided into four groups: females (fSHR), ovariectomized females (fSHR-OV), ovariectomized females with estrogen replacement (fSHR-OV+ES, 50 micrograms/kg SC 17 beta-estradiol benzoate every 48 hours), and males (mSHR). Arteriolar diameter in the presence of perfusion pressures of 60, 80, 100, and 120 mm Hg were obtained, and diameter changes were measured (at 80 mm Hg) in response to various concentrations of substance P (10(-9) to 5 x 10(-8) mol/L), sodium nitroprusside (10(-8) to 10(-6) mol/L), and A23187 (5 x 10(-8) to 10(-6) mol/L). The pressure-induced diameter of mSHR and fSHR-OV arterioles was significantly less (by approximately 10%) than that of fSHR and fSHR-OV+ES arterioles. N omega-nitro-L-arginine (10(-4) mol/L), a nitric oxide synthase inhibitor, elicited a significant decrease in basal arteriolar diameter of fSHR (by approximately 19%) and fSHR-OV+ES (by approximately 17%), thereby eliminating the differences in tone among the various groups. Dilations of fSHR and fSHR-OV+ES arterioles to substance P were significantly greater (by 140% at a concentration of 5 x 10(-8) mol/L) than those of mSHR and fSHR-OV arterioles, whereas dilations to sodium nitroprusside were not different among the groups. A23187 (a nitric oxide releaser) elicited dilations in arterioles of fSHR (5.9 +/- 1.5%, 13.0 +/- 1.8%, and 19.2 +/- 2.1%) and fSHR-OV+ES (4.3 +/- 1.0%, 10.3 +/- 2.4%, and 15.0 +/- 4.0%) but constrictions in those of mSHR (-7.5 +/- 1.6%, -25.3 +/- 39%, and -36.9 +/- 4.1%) and fSHR-OV (-2.6 +/- 1.7%, 7.4 +/- 3.3%, and -11.5 +/- 6.1%). We conclude that estrogen in fSHR is responsible for the preservation of nitric oxide synthesis in skeletal muscle arterioles, resulting in a greater modulation of pressure-induced myogenic tone than in mSHR and maintenance of nitric oxide-mediated dilations.

Animals↗
PubMed1997

Myogenic responses of isolated lymphatics: modulation by endothelium.

OBJECTIVE: To characterize the effect of increases of intraluminal pressure on the spontaneous diameter oscillations of isolated lymphatics and on the maximum and minimum diameter, in the presence and absence of endothelium. METHODS: Afferent lymphatics were isolated from rat iliac lymph nodes. After cannulation of both ends, lymphatics were equilibrated for 60 minutes at a pressure of 6 cm H2O, and then changes in diameter oscillations to increases in perfusion pressure (from 2-10 cm H2O, were measured. The endothelium was removed by intraluminal infusion of air. Changes in diameter were expressed as a percentage of the corresponding passive diameter obtained in Ca(2+)-free solution. RESULTS: Isolated lymphatics showed phasic spontaneous constriction and dilation (approximately 50 to approximately 150 microns). Removal of extracellular Ca2+ abolished spontaneous diameter oscillations, and the passive diameter increased from 183.0 +/- 5.3 to 205.1 +/- 8.8 microns as pressure increased from 2 to 10 cm H2O. In response to increases in pressure, the normalized minimum diameter (Dmin) increased (from 30.1% +/- 1.1% to 54.8% +/- 1.9% while the normalized maximum diameter (Dmax) of lymphatics did not change. With increasing pressure the amplitude of vasomotion (Dmax-Dmin) decreased, whereas the oscillation frequency increased. Removal of endothelium significantly reduced Dmax; hence, the oscillation amplitude decreased while the frequency increased. Also, endothelium removal elicited a significant change in the slope of the pressure-Dmax curve (from 0.01 +/- 0.4 to -1.43 +/- 0.34). CONCLUSIONS: Increases in intraluminal pressure greatly affect the spontaneous vasomotion of lymphatics and activate the myogenic mechanism intrinsic to the smooth muscle. In addition, endothelial factors are important to maintain adequate lymphatic vasomotion. These findings suggest that intraluminal pressure and endothelial factors can be important contributors to the tone and pumping activity of lymphatics in vivo.

Animals↗
PubMed1996

Regulation of nitric oxide production in human coronary microvessels and the contribution of local kinin formation.

BACKGROUND: The goal of this study was to define the regulation of nitric oxide release by coronary microvessels from the failing and nonfailing human heart and to determine the role of local kinin production in the elaboration of nitric oxide by human coronary microvascular endothelium. METHODS AND RESULTS: Ten hearts from humans with end-stage heart failure and two hearts from patients without heart failure were harvested at the time of orthotopic cardiac transplantation. Microvessels were sieved and the production of nitrite was determined by the Griess reaction. Microvessels were incubated in the presence of agonists for nitric oxide production (acetylcholine and bradykinin), which caused dose-dependent increases in nitrite, a response that was blocked by NG-nitro-L-arginine methyl ester and receptor-specific antagonists (atropine and HOE 140, respectively). In addition, the production of nitrite by microvessels from the failing heart appeared to be less than that produced by microvessels from the nonfailing heart. Incubation with norepinephrine or the alpha2-adrenergic agonist BHT 920 also caused dose-dependent increases in nitrite production, which were blocked by the B2-receptor antagonist HOE 140. This implicated local kinin synthesis as an intermediate step in the production of nitric oxide in response to alpha2-adrenoceptor stimulation. The production of nitric oxide was also prevented by the addition of serine protease inhibitors, which blocked the action of local kallikrein, again suggesting a role for local kinin synthesis. CONCLUSIONS: Our results indicate that nitric oxide is produced by human coronary microvessels, that nitric oxide production may be reduced but certainly not increased in microvessels from the failing human heart, and that there is active local kinin generation in these blood vessels.

Adult↗
PubMed1996

Neural regulation of coronary vascular resistance: role of nitric oxide in reflex cholinergic coronary vasodilation in normal and pathophysiologic states.

A number of reflexes participate in the control of coronary vascular resistance through activation of the sympathetic or parasympathetic nervous system. Classically, activation of vagal efferent fibers to the heart results in vasodilation due to the release of acetylcholine and activation of muscarinic receptors. Recently, we have found that activation of a number of reflexes in conscious dogs, the Bezold-Jarisch reflex and the carotid chemoreflex in particular, results in cholinergic coronary vasodilation which is blocked by an inhibitor of nitric oxide synthesis, nitro-L-arginine. After the development of pacing-induced heart failure, the cholinergic dilation subsequent to activation of the Bezold-Jarisch or carotid chemoreflex is essentially abolished, since coronary blood vessels no longer produce nitric oxide. In contrast, after brief exercise training, there is a potentiation of Bezold-Jarisch reflex-induced coronary vasodilation since exercise upregulates nitric oxide production by coronary blood vessels. Since the Bezold-Jarisch reflex may be important as a compensatory mechanism during acute myocardial infarction, and the carotid chemoreflex is the acute mechanisms responsible for ameliorating systemic hypoxemia, the role of nitric oxide in reflex cholinergic coronary vasodilation may be essential in the compensatory vascular adjustments evoked by these and other reflexes.

Animals↗
PubMed1996

Myogenic responses of isolated rat skeletal muscle venules: modulation by norepinephrine and endothelium.

The pressure-induced myogenic response of large venules of skeletal muscle and its possible interactions with adrenergic receptor activation and endothelial factors have not yet been elucidated. Therefore, first-order venules of rat gracilis muscle were isolated, cannulated, and placed in an organ chamber. Changes in internal diameter of the vessels as a function of perfusion pressure (PP) were obtained. In response to increases in PP (0.5-17.5 mmHg), the diameter of venules increased from 197.1 +/- 23.96 to 369 +/- 14.1 microns. In passive conditions (in Ca(2+)-free solution), the pressure-diameter curve of venules shifted significantly upward. In the presence of norepinephrine (NE; 10(-6) M) in the bath solution, the pressure-diameter curve of active venules shifted significantly downward, and in the pressure-normalized diameter curve, a negative slope developed (-6.1 +/- 4.6). In both the absence and presence of NE, removal of endothelium significantly reduced venular diameters in the pressure ranges of 3-5 and 2-5 mmHg, respectively, but did not change significantly the characteristics of the pressure-diameter curves. These findings indicate that the smooth muscle of venules actively responds to changes in intraluminal pressure. This response is greatly facilitated by NE and modulated by the endothelium. The myogenic response of skeletal muscle venules, especially in the presence of NE, could have a role in the regulation of the resistance and capacitance of venules and, consequently, blood flow and tissue exchange in skeletal muscle.

Animals↗
PubMed1995

Effects of Hoe-140 and ramiprilat on arteriolar tone and dilation to bradykinin in skeletal muscle of rats.

In skeletal muscle of pentobarbital sodium-anesthetized rats, the mechanism of action and possible role of the potent vasodilator bradykinin (BK) in regulation of arteriolar tone were investigated. Changes in diameter of third-order arterioles of cremaster muscle in response to topical administration of BK and other vasoactive agents were measured with an image-shearing monitor and recorded with video microscopy. All agonists were administered topically on the exteriorized muscle. With use of Hoe-140, a B2-receptor antagonist, the presence of kinin receptors in arterioles was studied. In control preparations, 10(-5) M arachidonic acid (AA), 0.5 x 10(-6) M acetylcholine (ACh), and 10(-5) M adenosine (ADO) evoked dilation of arterioles of up to 70% of resting diameter. BK (10(-9), 10(-8), 10(-7), and 10(-6) M) elicited dose-dependent arteriolar dilations (1.3 +/- 1.3, 4.1 +/- 0.5, 10.3 +/- 1.6, and 13.3 +/- 1.3 microns, respectively). In the presence of 10(-7) M Hoe-140, dilations to AA, ACh, and ADO were not affected, but those to 10(-9)-10(-7) M BK were eliminated or significantly inhibited (10(-6) M BK: to 2.9 +/- 1.8 microns). Also, whereas Hoe-140 significantly reduced basal arteriolar diameters (from 16.7 +/- 0.9 to 13.8 +/- 1.1 microns, P < 0.05), it did not affect constrictions to norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Exercise training augments flow-dependent dilation in rat skeletal muscle arterioles. Role of endothelial nitric oxide and prostaglandins.

We aimed to test the hypothesis that as a consequence of short-term daily exercise, flow (shear stress)-dependent dilation and its mediation by the endothelium are altered in skeletal muscle arterioles. After initial familiarization with the protocol, rats ran on a treadmill once a day (with gradually increasing intensity up to 40 minutes and 28 m/min) for approximately 3 weeks (EX group); a control group remained sedentary (SED group). The active (internal) diameters of isolated gracilis muscle arterioles of SED and EX rats at 80 mm Hg were significantly different (55.2 +/- 2.1 and 49.3 +/- 2.0 microns, P < .05), and their passive diameters (in Ca(2+)-free solution) were 105.3 +/- 3.1 and 111.2 +/- 2.4 microns (not significantly different), respectively. Increases in flow of the perfusion solution from 0 to 12 microL/min elicited a significantly greater increase in diameter of EX arterioles (by 83.5% at maximum flow). This enhanced sensitivity maintained a lower shear stress in EX arterioles (15 to 20 dyne/cm2) compared with SED arterioles (25 to 35 dyne/cm2). In both SED and EX arterioles, flow-dependent dilation was eliminated after removal of the endothelium. Either N omega-nitro-L-arginine, a nitric oxide synthase inhibitor, or indomethacin, an inhibitor of prostaglandin synthesis, shifted the flow-diameter and calculated wall shear stress-diameter curves significantly to the right. Each of the inhibitors reduced flow-dependent dilation to a similar degree (approximately 40% to 45%); their combined administration nearly completely eliminated the dilation of arterioles of both SED and EX rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1995

Flow-dependent dilation and myogenic constriction interact to establish the resistance of skeletal muscle arterioles.

OBJECTIVE: To test the hypothesis that the diameter of skeletal muscle arterioles is determined by the interaction of responses elicited by intravascular pressure and flow. METHODS: Experiments were conducted on isolated, cannulated, first-order arterioles of cremaster muscle of male Wistar rats. The diameter of arterioles was followed by videomicroscopy. Perfusion pressures and flows were controlled. RESULTS: In the absence of perfusate flow, increases in perfusion pressure (from 0 to 120 mm Hg), after initial dilation, elicited endothelium independent constrictions of arterioles. At 60 mm Hg of perfusion pressure, the active diameter of vessels was 84.9 +/- 1.9 microns. The passive diameter of arterioles (Ca2(+)-free solution)was 150.6 +/- 2.4 microns. Increases in perfusate flow resulted in a significant upward shift in the pressure-diameter curves; in the presence of perfusate flows of 20, 40, and 60 microL/min, the constriction of the vessels at a pressure of 60 mm Hg was attenuated by 25.1 +/- 3.9%, 35.2 +/- 3.0%, and 46.8 +/- 4.4%, respectively. In contrast, the corresponding diameter of arterioles at perfusate flows of 10 to 60 microL/min was significantly reduced when perfusion pressure was increased from 60 to 80 and 100 mm Hg (at a flow of 60 microL/min) by 12.0 +/- 4.3% and 37.1 +/- 2.8%, respectively. Hence, both flow- and shear stress-diameter curves were significantly shifted downward when perfusion pressure increased from 60 to 100 mm Hg. CONCLUSION: These results demonstrate that an interplay between pressure and flow-sensitive mechanisms is an important determinant of the arteriolar resistance in skeletal muscle.

Animals↗
PubMed1994

Increases in oxygen tension evoke arteriolar constriction by inhibiting endothelial prostaglandin synthesis.

In vivo and in vitro studies concerned with the role of oxygen in the regulation of blood flow have primarily investigated the response of blood vessels to decreases in oxygen tension. In this study, we examined the response of isolated rat cremaster skeletal muscle arterioles to increases in oxygen tensions. First-order arterioles with an average diameter of 90 microns were cannulated and pressurized to 65 mm Hg and studied under constant pressure in a no-flow state. Arterioles were equilibrated in a Krebs bicarbonate-buffered solution (ph 7.4) gassed with 21% O2, 5% CO2, 74% N2. Changes in arteriolar diameters were continuously measured and recorded in response to increases in bath PO2 (20 to 660 mm Hg). Arterioles were studied before and after either the removal of the endothelium or the administration of indomethacin (IND, 10(-5) M), to inhibit prostaglandin synthesis. When the bath PO2 was increased from 20 to 150 mm Hg, arteriolar diameters decreased by 37%; they then decreased an additional 14% when bath PO2 was increased from 150 to 660 mm Hg. Removal of the endothelium or administration of IND completely eliminated the arteriolar constrictions in response to increases in PO2 from 20 to 150 mm Hg, and from 150 to 660 mm Hg. These observations suggest that rat cremaster arterioles constrict to increases in oxygen tension by reduction in the synthesis of endothelium-derived dilator prostaglandins.

Animals↗
PubMed1994

Characteristics and origin of myogenic response in isolated gracilis muscle arterioles.

Responses to changes in intravascular pressure of isolated rat gracilis muscle arterioles were investigated under no-flow conditions. First-, second-, and third- order arterioles were isolated and cannulated. Vascular diameters were measured with an image-shearing device and then recorded. In response to the step increases in perfusion pressure (from 20 to 160 mmHg, by 10- or 20-mmHg steps) arterioles constricted and developed active tone. For example, at 100, 80, and 50 mmHg pressure the steady-state active diameters of 1st-, 2nd-, and 3rd-order arterioles were 76.9 +/- 1.6, 32.3 +/- 1.1 and 22.3 +/- 3.2 microns, respectively. At the same perfusion pressure, by use of a Ca(2+)-free solution (ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid; 1 mM) containing sodium nitroprusside (SNP; 10(-4) M), the passive diameters (PD) of these vessels were 161.8 +/- 3.2, 76.0 +/- 1.7, and 47.6 +/- 2.2 microns. The negative slopes of the pressure-diameter curves indicate that in the physiological pressure range an inverse relationship exists between the arteriolar diameter and intravascular pressure. The maximum constriction expressed as a percent of PD was similar in the various sized arterioles (approximately 60%) but was reached at lower pressures in the smaller vessels. The vasoactive function of endothelium and vascular smooth muscle was assessed by the responses of arterioles to acetylcholine (ACh; 10(-6) M) and SNP (5 x 10(-8) M) before and after removal of the endothelium with air. After removal of the endothelium, dilation to ACh was abolished while dilation to SNP was retained.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

Corelease of nitric oxide and prostaglandins mediates flow-dependent dilation of rat gracilis muscle arterioles.

We have studied the mechanisms responsible for the mediation of flow (shear stress)-induced dilation of isolated arterioles of rat gracilis muscle. Active diameter of arterioles at a constant perfusion pressure (PP, 80 mmHg) was approximately 92 microns, while their passive diameter (Ca(2+)-free solution) was approximately 165 microns. At a constant PP the stepwise increase in flow of the perfusion solution (PS, 0-60 microliters/min in 10-microliters/min steps) elicited a gradual increase in diameter up to approximately 140 microns. Flow-induced dilations were eliminated by the removal of the endothelium of arterioles (by air). Dilations were significantly reduced by the cyclooxygenase blocker, indomethacin (Indo, 10(-5) M), by the nitric oxide synthase blocker, N omega-nitro-L-arginine (L-NNA, 10(-4) M), or by the endothelium-derived relaxing factor inhibitor, oxyhemoglobin (Hb, 10(-5) M), as indicated by the significant changes in the slope of the regression lines of the flow-diameter curves. For example, during administration of the inhibitors, dilation to 60 microliters/min perfusate flow was reduced by 41.1, 54.3, and 39.3%, respectively. Combined application of Indo and L-NNA almost completely eliminated flow-induced dilation. Arteriolar dilation maintained calculated wall shear stress close to control values (approximately 30 dyn/cm2 at 60 microliters/min) despite increases in flow, but when the dilation was inhibited by removal of the endothelium or by the combined administration of Indo and L-NNA, wall shear stress was greatly increased as a function of increases in flow of the PS (approximately 125 dyn/cm2).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

Short-term daily exercise activity enhances endothelial NO synthesis in skeletal muscle arterioles of rats.

We aimed to test the hypothesis that as a consequence of short-term daily bouts of exercise the control of arteriolar smooth muscle by endothelium is altered. Rats ran on a treadmill once a day, 5 days/wk, for 2-4 wk (with gradually increasing intensity, up to 26 min at 22 m/min at a 1% grade by the beginning of the 3rd wk and up to 38 min at 28 m/min at a 2% grade by the beginning of the 4th wk) while a control group remained sedentary (SED). Cannulated and pressurized arterioles of rat gracilis muscle developed spontaneous myogenic tone, which was slightly enhanced in exercised (EX) compared with SED rat arterioles. At 80 mmHg pressure, the passive (Ca(2+)-free solution) and active diameters of SED and EX rat arterioles were 105.4 +/- 3.8 and 55.1 +/- 2.3 microns and 107.1 +/- 3.4 and 50.2 +/- 2.2 microns, respectively. Dose-dependent dilations to sodium nitroprusside (10(-8)-10(-6) M) and constrictions to norepinephrine (10(-8)-10(-6) M) were not affected in EX arterioles, whereas dilations to adenosine (10(-6)-10(-4) M) were significantly reduced. In contrast, dose-dependent dilations to acetylcholine (ACh; 5 x 10(-9)-10(-7) M) and L-arginine [precursor of nitric oxide (NO); 10(-4)-10(-3) M] were significantly enhanced (by 33-78 and 57-75%, respectively) in arterioles of EX compared with those of SED rats. Responses of arterioles to sodium nitrite were not different in SED and EX groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1993

L-arginine analogues blunt prostaglandin-related dilation of arterioles.

The effects of arginine analogues, inhibitors of endothelium-derived nitric oxide synthesis, on dilation of arterioles in response to various vasoactive substances were studied. At 65 mmHg intravascular pressure, isolated arterioles of rat cremaster muscle developed tone spontaneously and achieved control diameters similar to those observed in vivo (84.1 +/- 2.0 microns vs. passive diameter: 161.3 +/- 3.4 microns). Acetylcholine (ACh, 5 x 10(-8) M), sodium nitroprusside (SNP, 5 x 10(-8) M), arachidonic acid (AA, 10(-7) M), prostaglandin E2 (PGE2, 10(-9) M), and adenosine (ADO, 10(-6) M) were added to the Krebs bicarbonate buffer solution, suffusing the vessels. The peak vasodilator effects of all agents were studied before and after the administration of various doses of N omega-nitro-L-arginine (L-NNA; 10(-5), 10(-4), and 10(-3) M), which significantly reduced, in a dose-dependent manner, the basal diameter of arterioles by 3.6, 15.2, and 18.9%, respectively. The lowest concentration of L-NNA significantly inhibited arteriolar dilations to ACh by approximately 26%. Higher concentrations of L-NNA and N omega-monomethyl-L-arginine (L-NMMA; 10(-4) M) caused a further significant reduction in the dilation to ACh (to approximately 47%) and also significantly reduced dilator responses to AA and PGE2. In the presence of the highest concentration of L-NNA (10(-3) M), dilation to SNP and ADO were also significantly reduced. Removal of endothelium abolished dilation to ACh and AA but did not alter that to SNP, PGE2, or ADO.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1993

Role of shear stress and endothelial prostaglandins in flow- and viscosity-induced dilation of arterioles in vitro.

We have studied the effect of changes in shear stress on diameter of isolated arterioles of rat cremaster muscle. The steady-state active diameter of arterioles at a constant perfusion pressure (60 mm Hg) was 80 +/- 1.2 microns. The vessels' passive diameter (Ca(2+)-free solution) was 156 +/- 1.8 microns. Changes in shear stress were induced either by an increase in flow (velocity) or by an increase in viscosity of the perfusion solution. At a constant perfusion pressure, the stepwise increase in perfusion flow (0-80 microliters/min in 10-microliters/min steps) elicited, with a delay of approximately 20 seconds, a gradual increase in diameter up to 46%. At a constant 20-microliters/min flow rate, increases in viscosity of the perfusate (2%, 4%, and 6% dextran [molecular weight, 77,800]) caused a gradual vasodilation up to 22%. Varying flow and viscosity of the perfusate simultaneously resulted in an upward shift of the flow-diameter curve. Both flow- and viscosity-induced dilations were eliminated by the removal of the endothelium of arterioles (by air) or were inhibited by indomethacin (10(-5) M). The efficacy and specificity of these inhibitory treatments were assessed with vasoactive agents whose action, with regard to endothelial mediation, has been determined previously. The arteriolar dilation maintained calculated wall shear stress close to control values during increases in flow and/or viscosity of the perfusate, but when the dilation was inhibited by removal of the endothelium or by indomethacin, wall shear stress increased significantly in a cumulative manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Endothelium-dependent dilation to L-arginine in isolated rat skeletal muscle arterioles.

The vascular actions of L-arginine (L-Arg) were studied in isolated, pressurized first-order rat cremaster muscle arterioles (93 +/- 2.9 microns) bathed in a Krebs bicarbonate-buffered solution, pH 7.4, equilibrated with 21% O2-5% CO2. Arterioles were studied before and after either the administration of NG-nitro-L-arginine (L-NNA, 10(-3) M), an inhibitor of the synthesis of endothelium-derived relaxing factor (EDRF), or the removal of the endothelium. Acetylcholine (ACh, 10(-8) and 10(-6) M), sodium nitroprusside (SNP, 10(-8) M) and phenylephrine (PE, 10(-7) M) evoked dilation and constriction, respectively. L-Arg, (10(-5)-10(-3) M) the precursor of EDRF, evoked dose-dependent arteriolar dilation; whereas D-arginine (D-Arg, 10(-5)-10(-3) M) was without any significant effect. Administration of L-NNA significantly reduced basal diameters and significantly inhibited the arteriolar dilations to both ACh and L-Arg but had no effect on the dilation to SNP. Removal of the arteriolar endothelium with air inhibited dilations to both ACh and L-Arg, had no effect on responses to SNP, and potentiated vasoconstrictor responses to PE. These findings suggest that in skeletal muscle arterioles the dilations to ACh and L-Arg are endothelium dependent and that microvascular endothelium modulates constrictor responses to PE. Thus EDRF may play an important role in the local regulation of arteriolar resistance and blood flow.

Acetylcholine↗
PubMed1992

Regulation of arteriolar tone and responses via L-arginine pathway in skeletal muscle.

With in vivo television microscopy, changes in arteriolar diameter to topical administration of various vasoactive agents were examined in the absence or in the presence of NG-monomethyl-L-arginine (L-NMMA, topical 100 microM) or NG-nitro-L-arginine (L-NNA, 2.5 microM, 20 microliters/min ia), specific inhibitors of endothelium-derived relaxing factor (EDRF) biosynthesis. In cremaster muscle arterioles (15-22 microns) of rats (n = 6-11), dilations to acetylcholine (1-100 ng) were significantly inhibited (60-70%) by either of the arginine analogues. This inhibition was reversed by subsequent administration of 1 mM L-arginine. Dose-dependent constriction to norepinephrine was enhanced by L-NMMA. Indomethacin treatment reduced arteriolar dilation to bradykinin (BK, 1-100 ng), which was significantly inhibited by additional administration of L-NNA. Application of L-NNA first, followed by additional indomethacin, elicited similar results. Dilations to sodium nitroprusside and adenosine were not reduced in the presence of the inhibitors. L-NMMA or L-NNA caused no change in systemic blood pressure but elicited a significant reduction in arteriolar diameter; this effect was not reversed by 1 mM L-arginine. These data demonstrate the presence of an L-arginine pathway to produce EDRF (nitric oxide) in skeletal muscle microcirculation that mediates and/or modulates arteriolar responses to vasoactive agents and could contribute to the regulation of basal vascular tone.

Animals↗
PubMed1992

Characteristics and origin of myogenic response in isolated mesenteric arterioles.

Responses to changes in intravascular pressure of isolated rat mesenteric arterioles were investigated under no-flow conditions. First-, second-, third-, and fourth-generation arterioles were isolated and cannulated. Vascular diameters were measured with an image-shearing device and recorded. The arterioles (except for the first-generation vessels) developed spontaneous tone, corresponding to the step increases in intravascular pressure (from 20 to 160 mmHg, by 20-mmHg steps). For example, at 80 mmHg pressure the mean diameters of first-, second-, third-, and fourth-generation vessels were 286.9 +/- 5.0, 203.4 +/- 8.2, 92.5 +/- 4.6, and 35.6 +/- 4.8 microns, respectively; by use of a Ca(2+)-free solution containing ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (1 mM) and sodium nitroprusside (SNP; 10(-4) M) the passive diameters of these vessels were 295.6 +/- 6.3, 238.4 +/- 11.7, 120.3 +/- 3.7, and 59.4 +/- 3.1 microns, respectively, demonstrating that the degree of pressure-induced constriction increased with the increasing order of generations (3, 14, 24, and 43%, respectively). The vasoactive function of endothelium and vascular smooth muscle was assessed by the responses of arterioles to acetylcholine (ACh; 10(-6) M) and SNP (10(-7) M) before and after removal of the endothelium with air. After removal of the endothelium, dilation to ACh was abolished while dilation to SNP was retained. Removal of the endothelium did not significantly alter the changes in the diameter of arterioles in response to step increases in intravascular pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗