Abstract P079: Lymphatic Contraction Was Enhanced In Spontaneously Hypertensive Rats

Because lymph capillary network regulates interstitial electrolyte and volume balance, this system may function as regulating blood pressure (BP). Thus, changes in lymphatic activity can be expected to alter systemic BP. We recently reported that increasing BP caused lymphatic endothelial dysfunction via oxidative stress in hypertension. In this study, we examined lymphatic contractile function in thoracic duct from 10-14-week-old Wister-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). No distinct morphological difference was observed in thoracic duct isolated from WKY and SHR (n=4). Thoracic duct from SHR exhibited enhanced contractile response to serotonin (5-HT) or endothelin-1 (ET-1) compared to age-matched WKY (5-HT: 127.8±19.7% vs 53.6±10.3% of KCl-induced maximum contraction, p<0.05, n=5). The augmented contraction in SHR was diminished by fasudil, ROCK inhibitor (p<0.05, n=4-5). Consistent with this, increased phosphorylation of myosin phosphatase targeting protein (MYPT) was observed in SHR thoracic duct. Expression of ROCK1 or ROCK2 was not changed in SHR thoracic duct. Next we examined lymphatic contractile function in 4-week-old SHR showing normal BP. Contractile response to 5-HT or ET-1 was not enhanced in young SHR compared to age-matched WKY (n=4). To examine if lymphatic dysfunction was associated with increased BP, we treated 4-week-old SHR with antihypertensive drugs (hydrochlorothiazide and hydralazine) for 6 weeks. This treatment completely blocked elevation of systolic BP (SBP) in SHR (p<0.05, n=5), but did not prevent the augmentation of lymphatic contraction (5-HT: 99.0±7.2% vs 98.1±14.5%, n=5). Interestingly, treatment of young SHR with losartan (Angiotensin II type 1 receptor [AT1R] blocker) for 6 weeks ameliorated the augmented contraction (5-HT: 137.4±12.7% vs 77.9±8.8%, p<0.05, n=5), while this treatment scarcely diminished the increase in SBP (152.0±8.7 mmHg vs. 177.2±10.9 mmHg, p<0.05, n=5). We conclude that lymphatic contractile function was significantly enhanced in adult hypertensive SHR, which is mediated by RhoA/ROCK pathway thorough activation of AT1R. The increase in lymphatic constriction may be involved in increased BP in hypertension through decreased lymphatic compliance.