The Anthropocene is functionally and stratigraphically distinct from the Holocene.

Human activity is leaving a pervasive and persistent signature on Earth. Vigorous debate continues about whether this warrants recognition as a new geologic time unit known as the Anthropocene. We review anthropogenic markers of functional changes in the Earth system through the stratigraphic record. The appearance of manufactured materials in sediments, including aluminum, plastics, and concrete, coincides with global spikes in fallout radionuclides and particulates from fossil fuel combustion. Carbon, nitrogen, and phosphorus cycles have been substantially modified over the past century. Rates of sea-level rise and the extent of human perturbation of the climate system exceed Late Holocene changes. Biotic changes include species invasions worldwide and accelerating rates of extinction. These combined signals render the Anthropocene stratigraphically distinct from the Holocene and earlier epochs.

Chronic treatment with vascular endothelial growth factor preserves agonist-evoked vascular responses in the streptozotocin-induced diabetic rat.

AIMS/HYPOTHESIS: Vascular dysfunction is a hallmark of diabetes mellitus and endothelial dysfunction is considered to be a key early component of vascular dysfunction. Attenuated agonist-evoked responses are considered to be a barometer of endothelial/vascular dysfunction. We sought to determine whether vascular endothelial growth factor (VEGF) could prevent dysfunction from developing in the streptozotocin (STZ)-induced rat model of type 1 diabetes. MATERIALS AND METHODS: One week after induction of diabetes, STZ rats began a 4-week treatment protocol of twice-weekly i.v. injections of 2 microg VEGF or inactivated VEGF. Corresponding non-diabetic rats served as controls. Agonist-evoked vascular responses were recorded 1 day after the last treatment in anaesthetised rats. RESULTS: Acetylcholine (0.1-12.5 microg/kg) evoked increases in superior mesenteric arterial conductance and decreases in mean blood pressure, while methoxamine (12.5-100 microg/kg) and endothelin-1 (100-1,200 pmol/kg) evoked decreases in superior mesenteric arterial conductance and increases in mean blood pressure. These responses to all three agonists were attenuated in STZ rats, and chronic treatment with VEGF improved these responses dramatically. Both the reduction in plasma nitrate and nitrite and the elevation in aortic superoxide associated with STZ diabetes were normalised with VEGF treatment. VEGF also prevented the apparent paradoxical increased endothelial nitric oxide synthase expression seen in untreated STZ rats. CONCLUSIONS/INTERPRETATION: Chronic treatment with VEGF early in diabetes is able to prevent the attenuated agonist-evoked vascular responses in STZ rats and normalise the oxidative environment associated with the disease.

Breaking the sod: humankind, history, and soil.

For most of history, few things have mattered more to human communities than their relations with soil, because soil provided most of their food and nutrients. Accordingly, some of the earliest written documents were agricultural manuals intended to organize, preserve, and impart soil knowledge. Indeed, ancient civilizations often worshipped the soil as the foundry of life itself. For the past century or two, nothing has mattered more for soils than their relations with human communities, because human action inadvertently ratcheted up rates of soil erosion and, both intentionally and unintentionally, rerouted nutrient flows.

Endothelin antagonist reduces hemodynamic responses to vasopressin in DOCA-salt hypertension.

The contribution of endothelin to the changes in blood pressure, cardiac output, and total peripheral resistance evoked by arginine vasopressin and angiotensin II was investigated in deoxycorticosterone acetate (DOCA)-salt hypertensive rats by infusing the peptides intravenously before and after pretreatment with the endothelin receptor antagonist bosentan. Blood pressure was recorded with radiotelemetry devices and cardiac output was recorded with ultrasonic transit time flow probes in conscious unrestrained animals. The dose-related decreases in cardiac output induced by vasopressin and angiotensin II were unaffected by bosentan. In contrast, the dose-related increases in total peripheral resistance evoked by vasopressin were blunted in both DOCA-salt hypertensive and sham normotensive rats, but this effect of bosentan was greater in the DOCA-salt hypertensive group. In contrast with vasopressin, bosentan failed to change hemodynamic responses to angiotensin II. The exaggerated vascular responsiveness (total peripheral resistance) of the DOCA-salt hypertensive group to vasopressin was largely abolished by bosentan. These results suggest that endothelin contributes to the hemodynamic effects of vasopressin but not angiotensin II in the DOCA-salt model of hypertension.

Cysteinyl leukotrienes mediate enhanced vasoconstriction to angiotensin II but not endothelin-1 in SHR.

We assessed whether cysteinyl leukotrienes mediate the vasoconstrictor responses to angiotensin II and endothelin-1 in the mesenteric vascular bed of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) perfused ex vivo at a constant flow rate of 5 ml/min with Krebs buffer. Maximal perfusion pressure response (E(max)) but not EC(50) values to angiotensin II (P < 0.001) and endothelin-1 (P < 0.01) were significantly higher in the SHR, whereas the responses to potassium chloride remained unchanged. Inclusion of the selective 5-lipoxygenase inhibitor AA-861 or the cysteinyl leukotriene receptor antagonist MK-571 significantly reduced the vasoconstrictor responses to angiotensin II but not to endothelin-1 and potassium chloride. The reduction in E(max) to angiotensin II was more pronounced in SHR (P < 0.001) than in WKY (P < 0.05) rats. Cysteinyl leukotrienes LTC(4)-, LTD(4)-, and LTE(4) (1 microM)-evoked vasoconstrictor responses were significantly higher in SHR (P < 0.05), whereas LTB(4) failed to evoke any response in either strain. These data suggest that 5-lipoxygenase metabolites, particularly cysteinyl leukotrienes, contribute to the exaggerated vasoconstrictor responses to angiotensin II but not to endothelin-1.

Insulin-induced biphasic responses in rat mesenteric vascular bed: role of endothelin.

The vasodilatory capacity of insulin has been widely reported, yet some investigators have not noted this effect. Because insulin has been shown to enhance endothelin release, we speculated that endothelin could be attenuating insulin-evoked vasodilation. We examined the effect of ex vivo insulin perfusion on vascular resistance by using the Sprague-Dawley rat mesenteric vascular bed. In methoxamine-preconstricted preparations, insulin (3.0 pmol/L to 10 nmol/L) evoked a concentration-dependent decrease in perfusion pressure (PP) with a maximal response of 42.0+/-9.2%, whereas continuous exposure to 10 nmol/L insulin induced a 51.8+/-3.5% relaxation. Further exposure to 10 nmol/L insulin resulted in the generation of endothelin and a subsequent loss of the vasodilatory response. Indomethacin had no effect on vascular responses. The vasodilatory response was significantly inhibited by nitric oxide synthase inhibition (20.5+/-4.2%; P<0.01) and calcium-activated potassium channel blockade (28.5+/-3.7%; P<0.05). Endothelial denudation attenuated the vasodilatory component (20.3+/-7.1%; P<0.01) and altered the biphasic pattern of the response. The decline in insulin-evoked vasodilation was significantly prevented by an endothelin-A antagonist (BQ123), an endothelin-B antagonist (BQ788), and nonselective endothelin blockade with both BQ123 and BQ788. These results demonstrate that the endothelium is intimately involved in regulating the vascular response to insulin. Insulin promotes the release of nitric oxide and endothelium-derived hyperpolarizing factor. During sustained exposure to higher concentrations, this vasodilatory effect is countered by the pathological generation of endothelin. Endothelin receptor blockade facilitates the maintenance of vasodilation despite high insulin concentrations.

Role of endothelin and vasopressin in DOCA-salt hypertension.

1. The relative roles of endothelin (ET) and vasopressin (AVP) in the regulation of blood pressure (BP), cardiac output (CO) and total peripheral resistance (TPR) were investigated in the early stages (24 - 31 days) of development of hypertension in the conscious deoxycorticosterone acetate (DOCA)-salt hypertensive rat model. 2. BP was recorded with radiotelemetry devices and CO with ultrasonic transit-time probes. TPR was calculated from the BP and CO recordings. The contributions of endogenous ET and AVP were studied by infusing [d(CH(2))(5)(1),O-Me_Tyr(2),Arg(8)]-vasopressin, a V(1)-receptor antagonist, and bosentan, a mixed ET(A)/ET(B) receptor antagonist (Study 1). Vascular responsiveness was estimated from the changes in TPR evoked by i.v. infusions of ET-1 and AVP (Study 2). 3. In study 1, infusion of bosentan reduced TPR and BP dramatically in DOCA-salt hypertensive rats but not in SHAM control rats, and this effect was greater when the AVP system had been blocked. In contrast, the V(1) receptor antagonist alone failed to change TPR and BP in DOCA-salt hypertensive rats. However, subsequent infusion of the V(1) receptor antagonist during the plateau phase of the response in bosentan pretreated DOCA-salt hypertensive rats led to significant decreases in both BP and TPR. 4. In study 2, TPR and BP responses to ET-1, but not AVP, were greater in DOCA-salt rats than in control rats. CO responses to ET-1 or AVP were similar in the two groups. 5. The results suggest that both ET and AVP play a role in the maintenance of TPR and BP; when one system is blocked the other compensates. However, the magnitude of the contribution to the hypertensive state appears greater for ET than for AVP. Enhanced vascular responses to ET appear to contribute to this greater role.

Effect of losartan on angiotensin II-mediated endothelin and prostanoid excretion in humans.

Angiotensin II (Ang II) stimulates renal prostanoid and vascular endothelin-1 (ET-1) release. Most known Ang II effects are mediated by AT1 receptors. Our aim was to determine whether AT1 receptor activation mediates Ang II-evoked renal prostanoid and ET-1 release. Eleven healthy men were randomized in a crossover, double-blind fashion to receive 100 mg/day of losartan or matching placebo, for 8 days. Blood and urine were sampled before and after a 2-h infusion of Ang II at a rate previously determined to increase mean arterial pressure (MAP) by 25 to 30 mm Hg in each subject. After a 14-day washout, subjects received the alternate treatment. Pretreatment with losartan had little effect on baseline MAP, but increased plasma renin activity, and virtually eliminated the pressor response to Ang II infusion. Angiotensin II significantly increased prostanoid excretion after placebo; the prostanoid response to Ang II was even greater after losartan. Plasma ET-1 was not altered by Ang II infusion, with or without losartan. In contrast, urine ET-1 excretion rate decreased to 40% of baseline after Ang II but not after losartan pretreatment; losartan alone had no effect. We conclude that Ang II decreases renal ET-1 synthesis and release through the AT1 receptor. In contrast, Angiotensin II-mediated renal prostanoid synthesis does not require activation of AT1 receptors. These findings indicate that AT1 receptor antagonists could provide renal protection through indirect mechanisms.

Upregulation of neuronal nitric oxide synthase in skeletal muscle by swim training.

Exercise enhances cardiac output and blood flow to working skeletal muscles but decreases visceral perfusion. The alterations in nitric oxide synthase (NOS) activity and/or expression of the cardiopulmonary, skeletal muscle, and visceral organs induced by swim training are unknown. In sedentary and swim-trained rats (60 min twice/day for 3-4 wk), we studied the alterations in NOS in different tissues along with hindquarter vasoreactivity in vivo during rest and mesenteric vascular bed reactivity in vitro. Hindquarter blood flow and conductance were reduced by norepinephrine in both groups to a similar degree, whereas N(G)-nitro-L-arginine methyl ester reduced both indexes to a greater extent in swim-trained rats. Vasodilator responses to ACh, but not bradykinin or S-nitroso-N-acetyl-penicillamine, were increased in swim-trained rats. Ca(2+)-dependent NOS activity was enhanced in the hindquarter skeletal muscle, lung, aorta, and atria of swim-trained rats together with increased expression of neuronal NOS in the hindquarter skeletal muscle and endothelial NOS in the cardiopulmonary organs. Mesenteric arterial bed vasoreactivity was unaltered by swim training. Physiological adaptations to swim training are characterized by enhanced hindquarter ACh-induced vasodilation with upregulation of neuronal NOS in skeletal muscle and endothelial NOS in the lung, atria, and aorta.

Radiotelemetric monitoring of blood pressure and mesenteric arterial bed responsiveness in rats with streptozotocin-induced diabetes.

We investigated the changes in arterial blood pressure (BP) and of mesenteric arterial bed (MAB) responsiveness that accompany streptozotocin (STZ)-induced diabetes. BP was recorded by radiotelemetry in conscious animals before and during a 4-week period following induction of the diabetic state with STZ. At the end of this period, the MAB was isolated and perfused under constant flow conditions: perfusion pressure (PP, mmHg) was taken as an index of arteriolar tone. BP was lower (P < 0.05) in STZ-treated diabetic rats (82.9+/-5.0 mmHg) than in vehicle-treated rats (108.9+/-6.3 mmHg). Basal perfusion pressure of the MAB was lower in STZ-treated rats than in control rats and inhibition of nitric oxide (NO) synthesis with N(G)-nitro-L-arginine-methyl-ester and N(G)-nitro-L-arginine (100 microM each) failed to change this relationship. Increases in PP of MAB to phenylephrine (Phe), norepinephrine (NE), and potassium chloride (KCl) were reduced in STZ-treated rats compared with control rats. Inhibition of NO synthesis reduced responses to Phe, NE, and KCL in both STZ and control rats. The reduced responsiveness of STZ rats to Phe, NE, and KCl persisted after inhibition of NO synthesis. Acetylcholine (ACh) evoked relaxation of the MAB in a dose-dependent fashion. Maximal responses to ACh, but not sodium nitroprusside, were lower in STZ rats than in vehicle treated rats. Inhibition of NO synthesis reduced responses to ACh in both STZ and control rats. The reduced responsiveness of STZ rats to ACh persisted after inhibition of NO synthesis. The data demonstrate that STZ-induced diabetes is associated with a fall in blood pressure when pressure is recorded with radiotelemetry. The fall in blood pressure may be related to a non-specific decrease in responsiveness to vasoconstrictor stimuli mediated at least in part by NO-independent mechanisms. A decrease in responsiveness to endothelial dependent vasodilator mechanisms appeared insufficient to restore responsiveness to vasoconstrictor stimuli.

Vanadate-evoked relaxation of the perfused rat mesenteric vascular bed.

Sodium orthovanadate (SOV) can contract smooth muscle; however, little is known about its effect on the vascular endothelium. We compared the vasorelaxant effects of acetylcholine (ACh) and SOV in the preconstricted, isolated perfused mesenteric vascular bed (MVB) of Sprague-Dawley rats. The maximal relaxation response evoked by SOV (40-45%) was lower than ACh (92-94%) but the IC50 values were similar. At concentrations > 1 mM, SOV elevated the basal tone. Endothelial denudation resulted in a substantial reduction of relaxation responses to both agents, whereas either nitric oxide synthase (NOS) inhibitors or high KCl partially reduced the responses. A combination of NOS inhibitors along with either a calcium-activated potassium channel (KCa) blocker, tetrabutylammonium (TBA), or high KCI inhibited the responses to a similar extent as endothelium denudation. Neither clotrimazole nor TBA attenuated ACh responses; however, maximal responses to SOV in the presence of TBA or clotrimazole were reduced. Indomethacin had no effect on responses to either agonists. These results indicate that like ACh, SOV-mediated vasorelaxation of the MVB involves recruitment of both endothelial derived hyperpolarizing factor (EDHF) and endothelial derived nitric oxide (NO) and not vasodilator eicosanoids. As the relaxation to SOV was dose-dependent at a low concentration range, it is likely that vanadate is involved in the regulation of total peripheral resistance.

Altered paracrine effect of endothelin in blood vessels of the hyperinsulinemic, insulin resistant obese Zucker rat.

OBJECTIVE: Earlier, we reported that high insulin incubation in vitro leads to increased ETA receptor expression in cultured rat aortic smooth muscle cells (Diabetes 1998, 47: 934-944). Our later observation of enhanced endothelin-1 evoked vasoconstriction in aorta from the hyperinsulinemic obese Zucker rat indicated that this interaction might also be relevant in vivo. To further examine the relationship between insulinemia and endothelin, we characterized endothelin receptor expression and endothelin-1 peptide levels in vascular tissues and plasma from young and old obese Zucker rats. METHODS: 12 and 40-week-old Zucker obese and lean rats were used. Plasma endothelin-1 levels and endothelin-1 peptide content in the mesenteric artery and in the thoracic aorta were examined by radioimmunoassay. Messenger RNA levels of endothelin-1 peptide and ETA and ETB receptors were examined in the aortic and mesenteric vessels using RT-PCR. RESULTS: Obese rats from both age groups had significantly higher plasma levels of insulin (4-10 fold), total cholesterol (2-3 fold), triglycerides (10-fold), and glucose (approximately 1.5 fold) than their lean counterparts. There was a trend toward worsening lipoproteinemia and glycemia, but improved insulinemia with age in the obese rats. In association with these changes, obese rats exhibited attenuated endothelin-1 peptide and preproET-1 mRNA levels, but conversely elevated ETA and ETB receptor mRNA levels in both aortic and mesenteric vessels. CONCLUSION: These data suggest that vascular tissue from the metabolically dysregulated obese Zucker rat exhibits attenuated endothelin-1 peptide production and elevated endothelin receptor levels. Since elevated insulin levels have been linked to increased endothelin receptor expression, it is plausible that hyperinsulinemia upregulates endothelin receptors contributing to elevated vasoconstrictor responses to endothelin-1 in this model of obesity and hypertension.

Effect of sodium orthovanadate treatment on cardiovascular function in the hyperinsulinemic, insulin-resistant obese Zucker rat.

We recently demonstrated that oral vanadate treatment ameliorates exaggerated vasoconstriction in aortic tissue from the hyperinsulinemic/insulin resistant obese Zucker rat. It has been suggested that changes in large artery contractility might contribute to the development of hypertension in this strain. Thus we examined the effect of vanadate treatment (0.5 mg/ml, p.o.) on conductance and resistance vessel function as well as blood pressure (BP) in Zucker rats. Vasoconstrictor responses to endothelin-1 (ET-1) and methoxamine and vasodilator responses to acetylcholine in the aorta and perfused mesenteric vascular bed served as indices of conductance and resistance function, respectively. Separate groups were treated with insulin (12 mU/kg/min, s.c.) to determine its role in the actions of vanadate. Vanadate treatment reduced (2.5-fold; p < 0.05) elevated plasma insulin levels and abolished exaggerated aortic vasoconstriction in obese rats. Vasoconstrictor responses in the mesenteric bed, however, were similar between obese and lean rats, and were unaffected by vanadate. Vanadate did not affect elevated BP in obese rats and actually increased BP in the lean group. Insulin treatment per se failed to affect vasomotor function or BP in either strain, and acetylcholine-evoked relaxation was similar in all groups. We conclude that whereas vanadate overcomes exaggerated central artery contractility in obese Zucker rats, it fails to affect resistance vessel function or BP in this strain, and might conversely elevate BP in normotensive lean control rats. The vascular actions of vanadate in obese rats appear to occur independent of changes in plasma insulin or endothelial function.

Total peripheral conductance mediates antihypertensive effect of nonpeptide mixed endothelin receptor antagonist in deoxycorticosterone acetate-salt hypertensive rats.

The relative contribution of cardiac output (CO) and total peripheral conductance (TPC) to the changes in blood pressure (BP) evoked by an intravenous injection of bosentan, a nonpeptide mixed endothelin (ET) antagonist, were investigated in conscious unrestrained deoxycorticosterone acetate (DOCA)-salt hypertensive rats and sham-control rats. Blood pressure was recorded by radiotelemetry devices and CO by ultrasonic transit-time flow probes. Bosentan significantly reduced BP (from 141 +/- 3 to 111 +/- 3 mm Hg) and increased TPC (from 1.19 +/-0.1 to 1.72 +/- 0.2 mL/min/kg/mm Hg) in DOCA-salt hypertensive rats, but not in sham rats. An increase in CO opposed the BP-lowering effect of the antagonist. The results demonstrate that the role of ET receptors in the maintenance of the hypertensive state in the DOCA-salt model of hypertension is exerted at the level of the resistance vessels and not on factors that regulate cardiac output.

Vasopressin accelerates protein synthesis in neonatal rat cardiomyocytes.

Arginine vasopressin (AVP) has been shown to promote vascular smooth muscle cell hypertrophy and hyperplasia of fibroblasts. The present study examines the effect of AVP and endothelin-1 (ET-1) on protein, DNA, and RNA synthesis in primary cultures of serum deprived neonatal rat cardiomyocytes (RC) as assessed by changes in [3H] phenylalanine, [3H] thymidine, and [14C] uridine incorporation respectively. Both AVP and ET-1 evoked significant increases in protein synthesis in RC of 36 +/- 12% (p < 0.05) and 53 +/- 22% (p < 0.01) respectively. The stimulating action of AVP on [3H] phenylalanine incorporation was abolished by pretreatment with 2-nitro-4carboxyphenyl-N, N-diphenylcarbamate (NCDC), a phospholipase C (PLC) inhibitor. [14C] uridine incorporation was significantly higher in cells incubated with ET-1 (95 +/- 12%) but not AVP (9 +/- 11%). Neither AVP nor ET-1 significantly affected cell number or [3H]thymidine incorporation, suggesting a lack of a hyperplastic effect. AVP evoked an increase in [Ca2+]i levels (162 +/- 12 nmol/L from a basal value of 77 +/- 6 nmol/L) which was completely abolished by pretreatment with either NCDC or cyclopiazonic acid (sarcoplasmic reticulum (SR) Ca2+ pump inhibitor) but unaffected by ryanodine (ryanodine sensitive SR Ca2+ store depletor). Taken together, these data suggest that AVP, in a PLC dependent manner, both stimulates protein synthesis and augments [Ca2+]i release in RC from ryanodine insensitive (IP3 sensitive) Ca2+ stores. Thus, AVP may promote cardiac hypertrophy via direct effects on cardiomyocyte protein synthesis secondary to IP3 mediated [Ca2+]i release.

Plasma endothelin levels and vascular responses at different temporal stages of streptozotocin diabetes.

While alterations in the release and action of endothelial derived vasoactive factors such as endothelin- and endothelial derived relaxing factor (EDRF) occur in diabetes mellitus, the nature and direction of these changes is controversial. We examined the role of diabetes duration on endothelin- plasma levels and vasoconstrictor responses to endothelin-1 in aortic rings from streptozotocin-induced diabetic rats. Endothelin-1 plasma levels were attenuated at 2-weeks, but conversely elevated at 14-weeks, after diabetes induction. Similarly, maximal vasoconstriction to endothelin-1 in aorta was exaggerated in 2-week, but attenuated in 14-week diabetic rats. Also, sensitivity of aorta to endothelin-1 was enhanced in the 14-week group. Neither nitric oxide synthase inhibition with nitro-L-arginine-methyl-ester, nor endothelium removal affected alterations in maximal vasoconstriction, but both abolished changes in sensitivity to endothelin-1. Endothelium dependent (acetylcholine-evoked) vasorelaxation responses were attenuated in 14-week, but not 2-week, diabetic rats, while endothelium independent (sodium nitroprusside-evoked) responses remained unchanged. Together, these data indicate a deficiency in EDRF production in the 14-week group. Elevated plasma glucose and attenuated insulin levels were present in both groups, but plasma cholesterol and triglyceride levels were elevated only in 14-week rats. We conclude that differences in the pre-existing duration of diabetes differentially affect both plasma levels and action of endothelin-1. These changes might be linked to coincident diabetes duration dependent changes in EDRF production and plasma lipid levels. Such a shift in the production and action of endothelial derived relaxing and contracting factors might contribute to the characteristic early and late stage cardiovascular complications of diabetes mellitus.

Pneumadin-evoked intracellular free Ca2+ responses in rat aortic smooth muscle cells: effect of dexamethasone.

The direct vascular effect of pneumadin (PN) was determined by studying the changes in intracellular free calcium ([Ca2+]i) levels in cultured rat aortic smooth muscle cells maintained between the second and fifth passages. PN evoked a rapid, concentration-dependent, biphasic increase in [Ca2+]i. The [Ca2+]i level rose from a basal value of 108 nM to a maximum increase in peak value of 170 nM. Although the level of maximal [Ca2+]i response evoked by PN was less than with other vasoactive agonists, it was more potent (EC50 0.5 nM) than even endothelin-1 (EC50 3.1 nM). At concentrations > 100 nM, [Ca2+]i elevations induced by PN above basal levels were no longer observed. Pretreatment with dexamethasone (100 nM for 24 hr) resulted in a significant increase (P < 0.01) in the peak [Ca2+]i response (310 nM) to PN. However, the biphasic pattern in the peak [Ca2+]i responses encountered with increasing concentrations of PN remained unaffected. The exaggerated [Ca2+]i response to PN was abolished by preincubation of cells with either the glucocorticoid antagonist mifepristone (RU 486) or the protein synthesis inhibitor cycloheximide. Inclusion of either an AT1 antagonist (losartan), a V1 selective vasopressin antagonist (d(Ch2)5 Tyr (Me) AVP), or an alpha-adrenoceptor antagonist (phentolamine) failed to affect the increases in [Ca2+]i induced by PN. PN-evoked increases in inositol 1,4,5-trisphosphate levels paralleled the [Ca2+]i changes. These data suggest that PN increases Ca2+ mobilization in rat aortic smooth muscle cells via activation of phospholipase C coupled receptors. This effect is up-regulated by dexamethasone.

High flaxseed (linseed) diet restores endothelial function in the mesenteric arterial bed of spontaneously hypertensive rats.

The effect of high flaxseed diet (HFD) on blood pressure (BP) and mesenteric arterial bed (MAB) reactivity was studied in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. HFD did not affect BP in either SHR (control, 157 +/- 3; HFD, 153 +/- 3 mmHg) or WKY (control, 114 +/- 2; HFD, 117 +/- 2 mmHg) rats. Increases in perfusion pressure of the endothelium-intact MAB to phenylephrine and norepinephrine were higher (p < 0.05) in SHR than in WKY rats and the HFD failed to alter these responses. Vasorelaxant responses to acetylcholine (ACh) and bradykinin (BK) were greater (p < 0.05) in SHR maintained on HFD compared to SHR on control diet. While HFD also enhanced ACh responses in WKY, the effect was less than in SHR. Responses to sodium nitroprusside (SNP), were similar in all groups. Since ACh and BK-induced responses of the MAB were augmented in SHR on HFD, with no changes in BP, it is suggested that HFD improves endothelial vasorelaxant function through a pressure-independent mechanism.