PGH(2)-TxA(2)-receptor blockade restores vasoreactivity in a new rodent model of genetic hypertension

The purpose of this study was to determine whether activation of prostaglan din H-2-thromboxane A(2) (PGH(2)-TxA(2)) receptors impedes vasodilation in the in situ peripheral microcirculation of spontaneously hypertensive hamst ers, a new rodent model of high-renin genetic hypertension. Using intravita l microscopy, we found that vasodilation elicited by suffusion of acetylcho line and vasoactive intestinal peptide (VIP), two neurotransmitters localiz ed in perivascular nerves in the peripheral circulation, on the in situ che ek pouch was significantly attenuated in spontaneously hypertensive hamster s relative to age- and genetically matched normotensive hamsters (P < 0.05) . However, nitroglycerin-induced vasodilation was similar in both groups. P retreatment with SQ-29548, a selective and potent PGH(2)-TxA(2)-receptor an tagonist, restored acetylcholine- and VIP-induced vasodilation in spontaneo usly hypertensive hamsters. SQ-29548 had no significant effects on resting arteriolar diameter and on nitroglycerin-induced vasodilation in both group s. SQ-29548 slightly but significantly potentiated VIP- but not acetylcholi ne-induced vasodilation in normotensive hamsters. Collectively, these data indicate that activation of PGH(2)-TxA(2) receptors impedes agonist-induced vasodilation in the in situ cheek pouch of spontaneously hypertensive hams ters. We suggest that this model is suitable for studying the role of prost anoids in mediating vasomotor dysfunction observed in genetic hypertension.