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 prostaglandin H(2)-thromboxane A(2) (PGH(2)-TxA(2)) receptors impedes vasodilation in the in situ peripheral microcirculation of spontaneously hypertensive hamsters, a new rodent model of high-renin genetic hypertension. Using intravital microscopy, we found that vasodilation elicited by suffusion of acetylcholine and vasoactive intestinal peptide (VIP), two neurotransmitters localized in perivascular nerves in the peripheral circulation, on the in situ cheek pouch was significantly attenuated in spontaneously hypertensive hamsters relative to age- and genetically matched normotensive hamsters (P < 0.05). However, nitroglycerin-induced vasodilation was similar in both groups. Pretreatment with SQ-29548, a selective and potent PGH(2)-TxA(2)-receptor antagonist, restored acetylcholine- and VIP-induced vasodilation in spontaneously hypertensive hamsters. SQ-29548 had no significant effects on resting arteriolar diameter and on nitroglycerin-induced vasodilation in both groups. SQ-29548 slightly but significantly potentiated VIP- but not acetylcholine-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 hamsters. We suggest that this model is suitable for studying the role of prostanoids in mediating vasomotor dysfunction observed in genetic hypertension.
Suzuki
H
H
Department of Medicine, University of Illinois at Chicago, 60612-7323, USA.
Ikezaki
H
H
Hong
D
D
Rubinstein
I
I
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002610:Cheek / Q000098:blood supply; D006224:Cricetinae; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000037:antagonists & inhibitors*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011463:Prostaglandins H; D014665:Vasodilator Agents; D014660:Vasoactive Intestinal Peptide; D044262:Prostaglandin H2; D013928:Thromboxane A2; C045749:SQ 29548; D005996:Nitroglycerin; D000109:Acetylcholine