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W H Cline

Publications and source records attributed to W H Cline.

At least 19 recordsLinked to original sources
PubMed1991

Evidence for enhanced inhibitory modulation by cyclooxygenase products of noradrenergic neurotransmission in the mesenteric vasculature of young spontaneously hypertensive rats.

The effects of cyclooxygenase inhibition by indomethacin and meclofenamate on pre- and postjunctional aspects of noradrenergic neurotransmission were determined in mesenteric vascular preparations from 4- to 6-week-old spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKYs). Perfusion pressure responses to periarterial nerve stimulation and to exogenous norepinephrine (NE) were significantly greater in SHR than in WKY preparations, whereas fractional NE overflow was equivalent between the two strains. Indomethacin and meclofenamate enhanced perfusion pressure responses to periarterial nerve stimulation in both strains. Fractional NE overflow was significantly enhanced by indomethacin but only at 14 Hz in SHR preparations, whereas it was unaffected in WKY preparations. The combination of indomethacin and cocaine resulted in a significant enhancement of perfusion pressure responses to periarterial nerve stimulation in both strains that was significantly greater than that produced by either drug alone. This effect was significantly greater in SHR than in WKY preparations. This combination also resulted in a significant enhancement of responses to exogenous NE in both strains. Fractional NE overflow was significantly increased in SHR preparations in the presence of the combination of cocaine and indomethacin, whereas it remained unaltered in WKY preparations. These findings suggest that a cyclooxygenase product exerts both pre- and postjunctional inhibitory effects on vascular noradrenergic neurotransmission that differ in these two strains of rats. The prejunctional inhibitory effect of this cyclooxygenase product was observed only in SHR preparations and was especially evident in the presence of cocaine.

Animals↗
PubMed1989

Effect of moderate cooling on endogenous noradrenaline release from the mesenteric vasculature of rats.

1. Experiments were performed to investigate whether moderate cooling can reduce exocytotic noradrenaline release in the deep circulation of rats. 2. The release of endogenous noradrenaline from the entire mesenteric vasculature of the isolated intestine of rats was determined along with the perfusion pressure response to transmural field stimulation (TFS) (4-14 Hz) at 37 degrees C or 24 degrees C. 3. Although moderate cooling significantly augmented the perfusion pressure responses to TFS, it markedly depressed TFS-induced endogenous noradrenaline release. Moderate cooling also significantly reduced the perfusion pressure responses to exogenous noradrenaline. 4. Treatment of mesenteric vascular preparations with cocaine (10(-6) M) plus corticosterone (4 x 10(-5) M) to inhibit neuronal and extraneuronal noradrenaline uptake, respectively, significantly increased the TFS-induced pressor response at 37 degrees C, but not at 24 degrees C. 5. However, treatment with cocaine in combination with corticosterone significantly increased the TFS-induced release of noradrenaline at both temperatures. The enhancement produced by these uptake inhibitors on the TFS-induced noradrenaline release at 37 degrees C was significantly smaller than that observed at 24 degrees C. 6. These results indicate that moderate cooling can depress the exocytotic noradrenaline release in the mesenteric vasculature. However, it appears that reduced re-uptake by moderate cooling probably overcomes the inhibitory effect of cooling on the release of noradrenaline. 7. Thus, it is suggested that the increased pressor responses to TFS by moderate cooling are due, at least in part, to reduced uptake at lower temperatures.

Animals↗
PubMed1988

Effect of angiotensin III (des-Asp1-angiotensin II) on the vascular adrenergic neurotransmission in spontaneously hypertensive rats.

The effects of angiotensin III (des-Asp1-angiotensin II) on the pressor responses of the perfused mesenteric vascular bed to periarterial nerve stimulation (PNS) and exogenously administered noradrenaline (NA) of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were compared. Angiotensin III (10, 20, 30 and 50 ng/ml) induced a marked potentiation of the pressor response to PNS (8 Hz) in a concentration-dependent manner with a slight elevation of the basal perfusion pressure in both SHR and WKY. The facilitatory effect of angiotensin III was blocked by [Sar1,Ile8]angiotensin II (200 ng/ml) and did not significantly differ for SHR and WKY. Angiotensin III also potentiated the pressor response to infusion of NA (50 ng) to the same extent in SHR and WKY. The degree of potentiation of the response to NA was similar to that to PNS in both WKY and SHR. Perfusion of angiotensin III (50 ng/ml) did not alter the increase in the 3H-efflux evoked by PNS (8 Hz) in the perfused mesenteric vascular bed prelabelled with [3H]NA, whereas the peptide potentiated significantly the pressor response to PNS in WKY and SHR to the same extent. These results suggest that angiotensin III postsynaptically facilitates the adrenergic neurotransmission of the mesenteric vascular bed to the same extent in WKY and SHR.

Angiotensin II↗
PubMed1988

Reassessment of the blocking activity of prazosin at low and high concentrations on sympathetic neurotransmission in the isolated mesenteric vasculature of rats.

1. The overflow of endogenous noradrenaline from the rat mesenteric arterial vasculature was determined along with the perfusion pressure response to periarterial nerve stimulation (PNS) (4-12 Hz). 2. The PNS-induced pressor responses were blocked by prazosin at 3 X 10(-8) M but not by prazosin at 10(-6) M or the combination of prazosin at 3 X 10(-8) M and yohimbine (10(-7) M). 3. The PNS-induced overflow of endogenous noradrenaline was significantly augmented by prazosin at 10(-6) M or the combination of prazosin at 3 X 10(-8) M and yohimbine (10(-7) M) but not by prazosin at 3 x 10(-8) M alone. 4. The PNS-induced pressor response and endogenous noradrenaline overflow, in the absence of prazosin, were not significantly influenced by alpha, beta-methylene-adenosine triphosphate (alpha, beta-methylene ATP) (3 X 10(-6) M). The pressor responses to PNS which remained after prazosin at 10(-6) M were abolished by pretreatment with alpha, beta-methylene ATP and therefore attributable to coreleased ATP. 5. The pressor responses to exogenous noradrenaline were abolished by prazosin at both 3 X 10(-8) M and 10(-6) M. 6. These results suggest that no functionally significant amount of ATP was coreleased with noradrenaline by PNS in the presence of prazosin at low concentrations which blocked only postjunctional alpha 1-adrenoreceptors. 7. Thus, these results indicate that the effects of prazosin at high concentrations, such as 10(-6) M, on sympathetic neurotransmission should not be ignored when considering the mechanisms of vasoconstrictor responses to PNS following high concentrations of prazosin.

Adenosine Triphosphate↗
PubMed1988

Effects of propranolol and yohimbine on periarterial nerve stimulation-induced release of endogenous norepinephrine from the mesenteric vasculature of Wistar Kyoto and spontaneously hypertensive rats.

The overflow of endogenous norepinephrine (NE) from the mesenteric vasculature of the isolated mesentery of Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) was determined in response to periarterial nerve stimulation (PNS) before and after pretreatment with propranolol or yohimbine. Propranolol pretreatment did not significantly alter spontaneous NE overflow, total NE overflow, NE overflow/stimulus or fractional NE overflow in either WKY or SHR mesenteric vascular preparations at any of the PNS frequencies used. Yohimbine pretreatment did not significantly alter spontaneous NE overflow but did significantly increase total NE overflow, NE overflow/stimulus and fractional NE overflow at all PNS frequencies used in both WKY and SHR preparations. The magnitude of the effect of yohimbine on NE overflow/stimulus did not differ between WKY and SHR over the range of PNS frequencies used. The lack of effect of propranolol on NE overflow suggests that corelease of epinephrine is not sufficient to activate beta adrenergic receptor-mediated modulation of noradrenergic neurotransmission in either WKY or SHR mesenteric vascular preparations under the in vitro study conditions used. However, the effects of yohimbine indicate that prejunctional alpha-2 adrenergic receptor-mediated inhibition of noradrenergic neurotransmission is operative in both WKY and SHR mesenteric vascular preparations. These effects of yohimbine also suggest that no significant differences exist between the functional level of prejunctional alpha-2 adrenergic receptor-mediated autoinhibitory modulation of noradrenergic neurotransmission in mesenteric vascular preparations from adult WKY and SHR under the in vitro study conditions used.

Animals↗
PubMed1987

Parathyroid hormone-induced changes in cyclic nucleotide levels during relaxation of the rabbit [correction of rat] aorta.

Parathyroid hormone is a potent vasodilator in vivo and relaxes vascular tissue in vitro. Since parathyroid hormone action in kidney and bone is thought to be mediated by stimulation of cellular cyclic AMP production, the present study was designed to monitor changes in cyclic AMP and cyclic GMP in vascular tissue during relaxation by parathyroid hormone. Rabbit aortic strips were quick-frozen at various times after exposure to parathyroid hormone and the percent relaxation and cyclic nucleotide levels were determined. Cyclic AMP concentrations were elevated about 3-fold within 30 seconds after treatment with hormone. This corresponded to a 10% relaxation of the norepinephrine-contracted tissue. After five minutes, cyclic AMP was still elevated 2-fold above basal and the relaxation response was maximal (36%). The cyclic AMP and relaxation responses to parathyroid hormone were markedly potentiated by forskolin or methylisobutylxanthine. Parathyroid hormone produced a small but significant increase in cyclic GMP concentrations only at early time points whereas sodium nitroprusside substantially increased cyclic GMP and relaxed the strips at all times studied. The increase in cyclic AMP levels after exposure to parathyroid hormone occurred prior to or coincident with the onset of relaxation of the aortic strips. These findings are supportive of the hypothesis that the vascular actions of parathyroid hormone involve cyclic AMP.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Is presynaptic modulation of norepinephrine release altered in the mesenteric vasculature of adult spontaneously hypertensive rats?

There is a substantial body of indirect pharmacologic evidence which has been interpreted as indicating that presynaptic receptor-mediated modulation of noradrenergic vascular neurotransmission is altered in the mesenteric vasculature of SHR. Enhanced release of either total 3H or 3H-NE after prelabeling with 3H-NE has been demonstrated to occur from the mesenteric vasculature of SHR after administration of isoproterenol or angiotensin II. However, evidence has now been obtained in the mesenteric vasculature demonstrating that there are no differences in the release of endogenous NE from adult SHR preparations versus that from adult WKY preparations.

Animals↗
PubMed1987

Release of endogenous NE from the mesenteric vasculature of WKY and SHR in response to PNS.

The release of endogenous norepinephrine (NE) from the mesenteric vasculature of the isolated mesentery of Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) was determined in response to periarterial nerve stimulation (PNS). PNS caused a frequency-dependent release of NE that did not differ in WKY and SHR preparations at 4 to 10 Hz but was significantly greater from SHR preparations at 12 and 14 Hz. When expressed as NE release/stimulus, release was significantly greater from SHR preparations only at 14 Hz. Mesenteric vascular perfusion-pressure responses to PNS were significantly greater in SHR than in WKY preparations at 6 to 14 Hz. Mesenteric vascular perfusion-pressure responses to exogenous NE were significantly greater in SHR than in WKY preparations at all doses tested. Treatment of mesenteric vascular preparations from WKY and SHR with cocaine at two concentrations plus corticosterone to inhibit neuronal and extraneuronal NE uptake, respectively, increased PNS-induced overflow of NE significantly. There was no difference in the NE release/stimulus in response to PNS between WKY and SHR preparations after either concentration of cocaine. The enhanced PNS responses in SHR at higher frequencies appear to be due in part to decreased NE uptake.

Animals↗
PubMed1986

Endothelium-independent linkage of parathyroid hormone receptors of rat vascular tissue with increased adenosine 3',5'-monophosphate and relaxation of vascular smooth muscle.

We examined the mechanisms involved in the relaxation of rat vascular smooth muscle by PTH. PTH increased intracellular cAMP 10-fold in cultured vascular smooth muscle cells from rat aorta. Forskolin, methylisobutylxanthine, and papaverine all potentiated PTH action. The cAMP responses to PTH were not altered by concurrent addition of propranolol, phentolamine, atropine, or [Sar1,Ile8]angiotensin II. Only the synthetic PTH antagonist analog [Nle8,Nle18,Tyr34] bovine PTH-(3-34) inhibited the cAMP and vascular relaxation responses to PTH. Isoproterenol produced increases in intracellular cAMP and adenylate cyclase activity which were additive to those produced by PTH. In contracted rat aortic strips, PTH caused a dose-dependent relaxation which was not altered by removal of the vessel intima or treatment with nordihydroguaiaretic acid. Also, membrane preparations from intact aortas or aortas with the endothelium or adventitia removed displayed identical PTH-stimulated adenylate cyclase activities. These findings indicate that the relaxant action of PTH in rat aorta does not require an intact endothelium and results from a direct effect on the vessel medial layer. Relaxation appears to be mediated by a receptor unique for PTH which is linked to the adenylate cyclase of vascular smooth muscle cells.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Vasodilation of the rat mesenteric vasculature by parathyroid hormone.

The isolated, perfused rat mesenteric vascular bed was used as a sensitive model of resistance vessel dynamics to evaluate the vascular actions of parathyroid hormone (PTH). Periarterial sympathetic nerve stimulation (PNS) was carried out at 8 Hz, 2 msec in pulse duration (supramaximal voltage) for 30 sec. The pressor response to PNS was decreased in a dose-dependent fashion by synthetic bovine PTH(1-34). Reduction of the PNS response was greater than 30% at 30 nM PTH. The concentration of PTH required to produce a half-maximal (ED50) decrease in PNS-induced tone was 4 nM. The phosphodiesterase inhibitor, methylisobutylxanthine, at 300 nM did not alter the PNS response when given alone, but potentiated PTH action. Isoproterenol (1 microM) decreased the PNS response by only 20%. Propranolol (1 microM) inhibited the effect of isoproterenol on the PNS response, but not that of PTH. The inhibitory analog of PTH, bPTH(7-34), blocked PTH action completely only at 30- to 50-fold higher concentrations than that of PTH. PTH also decreased the pressor response to norepinephrine infusion, similar to the effects on PNS. Again, bPTH(7-34) blocked the actions of PTH on norepinephrine vasoconstriction. These findings indicate that PTH has greater efficacy and potency for reducing PNS pressor activity in the mesenteric vasculature than isoproterenol and demonstrate that PTH has significant vascular effects at nanomolar concentrations.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Endothelial modulation of vascular relaxation to nitrovasodilators in aging and hypertension.

Blood vessel responses to relaxant drugs have been reported to change with aging and with the development of hypertension. In view of the requirement of endothelial cells for the activity of many relaxant drugs, we examined the role of the endothelium in the relaxation response of vascular tissue. Aortic and mesenteric ring segments from normotensive and hypertensive rats, ages 5 to 6, 15 to 18 and 30 to 31 weeks, were examined for relaxation to sodium nitroprusside, sodium nitrite, atrial natriuretic factor and 8-bromo-cyclic GMP. Relaxation responses to the nitrovasodilators were reduced progressively with aging in ring segments of Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) with intact endothelium; however, intact SHR ring preparations displayed less relaxation to nitrovasodilators at 15 to 18 and 30 to 31 weeks than those of WKYs. Rubbed (endothelium denuded) ring preparations displayed greatest relaxation to nitrovasodilators with no difference being observed between SHR and WKY preparations at any age tested. Relaxation to atrial natriuretic factor and 8-bromo-cyclic GMP was not different between rubbed and unrubbed ring segments or between SHRs and WKYs, indicating no detectable impairment of the overall relaxation response in the vascular smooth muscle of SHRs. These results suggest that the total functional capacity of vascular smooth muscle to relax to nitrovasodilators is not changed with aging or hypertension. However, the endothelial cells exert modulatory influences upon the vascular smooth muscle to reduce overall responsiveness to nitrovasodilators, an effect that is enhanced with aging and the development of genetic hypertension.

Aging↗
PubMed1985

Enhanced in vivo responsiveness of presynaptic angiotensin II receptor-mediated facilitation of vascular adrenergic neurotransmission in spontaneously hypertensive rats.

Presynaptic angiotensin II (AII) receptor-mediated facilitation of vascular adrenergic neurotransmission was studied in the in situ, blood-perfused mesentery of 13- to 16-week-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar Kyoto rats (WKY). Mesenteric arterial perfusion pressure frequency-response curves to periarterial adrenergic nerve stimulation (PNS) and dose-response curves to exogenous norepinephrine (NE) were obtained in SHR and WKY. The effects of the following treatments on the mesenteric vascular perfusion pressure responses (PPR) to PNS and NE were studied: All alone infused i.a. at 1 and 5 ng/min; All infused at 5 ng/min after [Sar1-lle8]All infused at 20 ng/min; [Sar1-lle8]All infused at 20 ng/min alone; captopril alone at 0.1 mg/kg i.v.; All infused i.a. at 0.3 and 1 ng/min after captopril at 0.1 mg/kg and angiotensin I injected at 3 dose levels after captopril at 0.1 mg/kg. Control PPR to PNS and NE were greater in SHR than in WKY. Comparisons of PPR in SHR to those in WKY were made, therefore, at the predetermined PPR levels of 15, 20, 30, 40, 50, 60 and 70 mm Hg. All alone shifted the PNS frequency-response curve to the left to a greater extent in the SHR than in the WKY when infused at 5 ng/min but not when infused at 1 ng/min. Both infusion rates of All had significantly different effects on the dose-response curves to NE in WKY and SHR. The effects of All infusion (5 ng/min) on both the response to PNS and to NE were antagonized completely by the concurrent infusion of [Sar1-lle8] All at 20 ng/min.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1984

Involvement of the vascular renin-angiotensin system in beta adrenergic receptor-mediated facilitation of vascular neurotransmission in spontaneously hypertensive rats.

This study was conducted to investigate the possible involvement of the vascular renin-angiotensin system in the isoproterenol (ISO)-induced facilitation of adrenergic neurotransmission in the mesenteric vasculature. The isolated, perfused mesenteric vascular beds from normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were used for these studies. ISO at concentrations from 10(-9) to 10(-6) M caused significantly greater enhancement of the pressor response to periarterial nerve stimulation (PNS) in preparations from SHR than in those from WKY. The pressor responses to exogenous norepinephrine (NE) were, however, inhibited by ISO to a similar degree in preparations from both WKY and SHR. The enhancement of the PNS response produced by ISO was markedly attenuated by propranolol at 5 X 10(-7) M (nonselective beta receptor blocker) and by ICI 118,551 at 5 X 10(-7) M (selective beta-2 receptor blocker), whereas practolol at 5 X 10(-6) M (selective beta-1 receptor blocker) caused a potentiation of the ISO-induced enhancement of responses to PNS in preparations from both WKY and SHR. All three beta blockers generally abolished the ISO-induced inhibition of the pressor responses to exogenous NE. The selective beta-2 adrenergic receptor agonists, salbutamol (3 X 10(-8) to 3 X 10(-7) M) and terbutaline (10(-7) to 3 X 10(-7) M), caused significantly greater enhancement of the PNS response in preparations from SHR than in those from WKY, whereas the selective beta-1 agonist, dobutamine, caused only inhibition of the PNS responses in preparations from both WKY and SHR. These three agonists all tended to reduce the pressor responses to exogenous NE. The ISO-induced enhancement of the responses to PNS was also significantly reduced by either captopril (5 X 10(-6) M) or [Sar1-Ile8]angiotensin II (5 X 10(-7) M) in preparations from SHR. Neither captopril nor [Sar1-lle8] angiotensin II had an effect on the pressor response to NE infusion or on the ISO-induced inhibition of NE responses. Angiotensin I produced an enhancement of the pressor responses to PNS and to NE infusion with the effect being greater on the response to PNS than to NE in the preparations from SHR but not in those from WKY. This enhancement of the PNS response by angiotensin I was abolished by either captopril (5 X 10(-7) M) or [Sar1-Ile8]angiotensin II (5 X 10(-7) M) in preparations from both WKY and SHR.(ABSTRACT TRUNCATED AT 400 WORDS)

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1982

Enhanced angiotensin-mediated facilitation of adrenergic neurotransmission in spontaneously hypertensive rats.

The effect of angiotensin II on the pressor response of the mesenteric vascular bed to periarterial adrenergic nerve stimulation (PNS) was compared between spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Angiotensin II (1-20 ng/ml) caused a marked potentiation of the vasoconstrictor response to PNS (8 Hz, 2 msec, for 30 sec) in a concentration-dependent manner without significantly affecting the base-line perfusion pressure in either WKY or SHR. The facilitatory effect of angiotensin II was significantly greater in SHR than in WKY preparations. The effective concentration for the peptide in SHR was approximately one-third of that found in WKY. Angiotensin II also potentiated the pressor response to exogenously administered norepinephrine (NE, 50 ng) in both WKY and SHR. The degree of potentiation of the response to PNS was greater than that to NE in SHR, while this differential was found only at high concentrations of angiotensin II on the WKY. The facilitatory effect of angiotensin II on the pressor response to either PNS or NE was markedly reduced by [Sar1-Ile8]angiotensin II (200 ng/ml) in both WKY and SHR. Angiotensin II caused further potentiation of the vasoconstrictor response to PNS or NE infusion in the presence of cocaine (5 micrograms/ml), which was of a greater magnitude in SHR than in WKY. These results suggest that the presynaptic facilitatory modulation of adrenergic vascular neurotransmission, mediated by angiotensin II receptors, is enhanced in the perfused mesenteric vascular bed of SHR.

Angiotensin II↗
PubMed1981

Role of released catecholamines in the vascular response to injected angiotensin II in the dog.

The contribution of released epinephrine and norepinephrine to the pressor response induced by i.v. injected angiotensin II was assessed in pentobarbital-anesthetized dogs. Control pressor dose-response curves for i.v. angiotensin II were obtained in dogs pretreated with hexamethonium, atropine and practolol. Hexamethonium and atropine minimized the cardiovascular reflex responses elicited by the pressor action of angiotensin II which would preclude interpretation of the results. Practolol was administered to antagonize indirect cardiac stimulation selectively through sympathoadrenal activation by angiotensin II. Three additional pressor dose-response curves for angiotensin II were obtained in each dog. The second dose-response curve was obtained after the administration of phentolamine and the third dose-response curve was obtained after the subsequent administration of sotalol. The final dose-response curve was obtained after partial recovery of the pressor responsiveness to norepinephrine and epinephrine from phentolamine blockade. The pressor responses for angiotensin II after phentolamine and sotalol (curve 3) were significantly smaller than those in the control dose-response curve (curve 1). No significant differences in the pressor responses to angiotensin II were noted after phentolamine when compared with those obtained after phentolamine plus sotalol (curve 2 vs. curve 3). The angiotensin II pressor responses after partial recovery from phentolamine (curve 4) did not differ significantly from those obtained in the control dose-response curve. These results of released catecholamines mediated through alpha adrenergic receptors in the pressor response to angiotensin II.

Adrenal Medulla↗
PubMed1980

Diminished purinergic modulation of the vascular adrenergic neurotransmission in spontaneously hypertensive rats.

The inhibitory effects of adenosine and ATP on the pressor response of the perfused mesenteric vascular bed to perivascular adrenergic nerve stimulation were compared between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKR). Both adenosine and ATP inhibited the neurogenic vasoconstriction in a dose-dependent manner in WKR, in which the inhibitory effect of adenosine was approximately eight times greater than that of ATP on the basis of 50% inhibitory doses (ID50). In the same preparation isolated from SHR, the inhibitory effects of both adenosine and ATP were significatly smaller than that in WKR. The ID50 values in the SHR for both agonists were approximately six times those found in WKR. These compounds also inhibited the pressor response to norepinephrine (0.3 microgram/ml) infusion, but the degrees of inhibition were markedly less than those with the neurogenic pressor response, and were not significantly different between WKR and SHR. These results suggest that presynaptic inhibition of vascular adrenergic neurotransmission by purine compounds is reduced in SHR.

Adenosine↗