The dorsomedial hypothalamus (DMH) plays a strain-dependent role in vascular responses to cocaine but not cold stress in conscious rats

      We demonstrated that cocaine or cold water stress (CWS) elicits systemic vasoconstriction in Brown-Norway (BN) rats but an increase in cardiac output in Dahl salt sensitive (DSS) rats. Since the DMH plays an important role in stress responsiveness, we sought to determine the role of the DMH to these disparate stressors on regional vascular hemodynamics. We hypothesized that inhibition of the DMH would attenuate greater hindquarters vasoconstriction to either stress in BN compared to DSS rats. BN and DSS rats were instrumented for determination of arterial pressure, heart rate, and with pulsed Doppler flowprobes on the superior mesenteric and abdominal aorta. Bilateral guide cannulas were implanted above the DMH. After recovery, we observed that cocaine (5 mg/kg, iv) elicited greater hindquarters and mesenteric vasoconstriction and greater bradycardia in BN rats compared to DSS rats. In contrast, CWS (1 cm deep for 1 min) elicited tachycardia in all rats and greater increases in mesenteric resistance in BN rats but hindquarters vasodilation that was greater in BN compared to DSS rats. Therefore, visceral and skeletal muscle vascular responses differed between strains and stressors. We examined the dependence of these responses on the DMH with bilateral microinjections of muscimol (80 pmol in 100 nl) in the DMH. Muscimol attenuated the greater hindquarters and mesenteric vasoconstriction and tachycardia in BN rats without affecting responses in DSS rats in response to cocaine. Responses to CWS were unaffected by muscimol except that tachycardia was selectively reduced in BN rats. Kainate (10 pmol) in the DMH elicited a similar response pattern as CWS. These studies demonstrate that the DMH plays a strain- and stimulus-dependent role in mediating hemodynamic responses to stress. Our data suggest that there are significant variations in central neural pathways mediating stress that vary in different rat strains.
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