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Background and purpose: Angiotensin type 2 receptor (AT(2) receptor) stimulation evokes vasodilator effects in vitro and in vivo that oppose the vasoconstrictor effects of angiotensin type 1 receptors (AT(1) receptors). Recently, a novel non-peptide AT(2) receptor agonist, Compound 21, was described, which exhibited high AT(2) receptor selectivity. Experimental approach: Functional cardiovascular effects of the drug candidate Compound 21 were assessed, using mouse isolated aorta and rat mesenteric arteries in vitro and in conscious spontaneously hypertensive rats (SHR). Key results: Compound 21 evoked dose-dependent vasorelaxations in aortic and mesenteric vessels, abolished by the AT(2) receptor antagonist, PD123319. In vivo, Compound 21 administered alone, at doses ranging from 50 to 1000 ng center dot kg-1 center dot min-1 over 4 h did not decrease blood pressure in conscious normotensive Wistar-Kyoto rats or SHR. However, when given in combination with the AT(1) receptor antagonist, candesartan, Compound 21 (300 ng center dot kg-1 center dot min-1) lowered blood pressure in SHR only. Further analysis in separate groups of conscious SHR revealed that, at a sixfold lower dose, Compound 21 (50 ng center dot kg-1 center dot min-1) still evoked a significant depressor response in adult SHR (similar to 30 mmHg) when combined with different doses of candesartan (0.01 or 0.1 mg center dot kg-1). Moreover, the Compound 21-evoked depressor effect was abolished when co-infused (50 mu g center dot kg-1 center dot min-1 for 2 h) with the AT(2) receptor antagonist PD123319. Conclusion and implications: Collectively, our results indicate that acute administration of Compound 21 evoked blood pressure reductions via AT(2) receptor stimulation. Thus Compound 21 can be considered an excellent drug candidate for further study of AT(2) receptor function in cardiovascular disease.

Quantitative trait loci (QTLs) for a number of agronomically important traits of perennial ryegrass (Lolium perenne L.) were identified using a reference molecular marker-based genetic map. Replicated phenotypic data was obtained for a number of field-assessed morphological and developmental traits as well as the winter hardiness-associated characters of winter survival and electrical conductivity. Marker-trait association analysis was performed using a number of methods, and a high degree of congruence was observed between the respective results. QTLs were detected for morphological traits such as plant height, tiller size, leaf length, leaf width, fresh weight at harvest, plant type, spikelet number per spike and spike length, as well as the developmental traits of heading date and degree of aftermath heading. A number of traits were significantly correlated, and coincident QTL locations were identified. No significant QTLs for winter survival in the field were identified. However, a QTL for electrical conductivity corresponding to frost tolerance was located close to a heading date QTL in a region that may show conserved synteny with chromosomal regions associated with both winter hardiness and flowering time variation in cereals. The QTL analysis of multiple phenotypic traits provides the basis for marker assisted selection (MAS) of important agronomic characters, allowing genetic improvement of yield, quality and adaptation in perennial ryegrass breeding.