Osteoblast activity is diminished in young Spontaneously Hypertensive Rats

Spontaneously Hypertensive Rats (SHR) are used as a genetic model of essential hypertension. Reductions in cortical and cancellous bone mass and increased bone turnover have been observed in aged SHR vs. Wistar-Kyoto (WKY) rats, normotensive genetics controls. In addition, antihypertensive aids have been effective in improving bone parameters in hypertensive rats. Thus, the relation between hypertension and bone remodeling warrants further attention. The purpose of this study was to determine how acute (i.e., 9 weeks) hypertension effects bone remodeling parameters (i.e., osteoclast and osteoblast activity). Methods: Right femora from 14-week-old SHR (n=5) and WKY (n=4) rats were dissected, fixed in 10% formalin and processed for bone histomorphometry for the examination of bone microarchitectural (bone volume/total volume ratio [BV/TV, %], trabecular thickness [Tb.Th, μm], trabecular number [Tb.N /mm] and trabecular separation [Tb. Sp, μm]) and bone static (osteoid surface/bone surface [OS/BS, %], osteoblast surface/bone surface [Ob.S/BS, %], number of osteoblast per total area [N.Ob/T.Ar], osteoclast surface/bone surface [Oc.S/BS, %)], and number of osteoclast per total area [N.Oc/T.Ar]) properties. Results: Body mass did not differ between SHR and WKY rats (i.e., 357 ± 6g vs. 351 ± 8g). No significant differences in bone microarchitectural properties (i.e., BV/TV, Tb.Th, Tb.N and Tb.Sp) were observed after acute hypertension. However, OS/BS, which represents newly formed yet unmineralized bone tissue, was significantly (p \u3c 0.05) reduced in SHR vs. WKY rats. In addition, osteoblast activity (Ob.S/BS) was significantly (p \u3c 0.05) diminished with hypertension. Further, there was a tendency (p = 0.08) for higher N.Oc/T.Ar in SHR vs. WKY rats. Conclusions: Results from this study indicate that hypertension alters bone remodeling parameters by decreasing osteoblast and increasing osteoclast activity. Differences in bone mircoarchitectural properties (i.e., BV/TV, Tb.Th, Tb.N and Tb.Sp) were not observed at this age; however, the alterations in bone cellular activity (i.e., OS/BS, Ob.S/BS and N.Oc/T.Ar) imply that reductions in bone mass are inevitable as the duration of hypertension increases

Modulation of synaptic transmission to second-order peripheral chemoreceptor neurons in caudal nucleus tractus solitarius by α1adrenoreceptors. The Journal of Pharmacology and Experimental Therapeutics

ABSTRACT Norepinephrine (NE) is an important neurotransmitter in central autonomic regulation. Peripheral chemoreceptor stimulation activates central noradrenergic structures. These structures innervate and therefore could modulate neurons in caudal nucleus tractus solitarius (cNTS), which receives the first central projections from peripheral chemoreceptors. However, the role of ␣ 1 -adrenoreceptors in synaptic transmission of peripheral chemoreceptor inputs in cNTS is unknown. We investigated the responses to activation of ␣ 1 -adrenoreceptors on glutamatergic and GABAergic inputs in NTS slices using whole-cell recording. Second-order neurons were identified by 1,1Ј-dilinoleyl-3,3,3Ј,3Ј-tetra-methylindocarbocyanine, 4-chlorobenzenesulphonate (DiA) labeling of carotid bodies. Electrical stimulation of ipsilateral tractus solitarius was used to evoke excitatory postsynaptic currents (eEPSCs), whereas inhibitory postsynaptic currents were evoked (eIPSCs) by electrically stimulating NTS near the recorded neuron. Application of ␣ 1 -adrenoreceptor agonist phenylephrine (PE) at 20 M significantly decreased amplitudes of eEPSCs (78 Ϯ 1% of control; n ϭ 16; p Ͻ 0.01), and it increased amplitudes of eIPSCs (120 Ϯ 13% of control; n ϭ 7; p Ͻ 0.01). Both effects were blocked by the ␣ 1 -adrenoreceptor antagonist prazosin at 10 M. PE did not change holding current, input resistance, and current-voltage relationship in cNTS neurons. PE significantly changed paired pulse ratios of eEPSC/eIPSCs, increased the frequency of miniature IPSCs (329 Ϯ 10% of control; n ϭ 6; p Ͻ 0.05), but it decreased that of miniature EPSCs (69 Ϯ 6% of control; n ϭ 5; p Ͻ 0.01). PE-induced inhibition of eEPSCs was independent of N-methyl-D-aspartate or GABA B receptors. These results suggest that activation of ␣ 1 -adrenoreceptors reduces excitatory and enhances inhibitory inputs to second-order peripheral chemoreceptor neurons in cNTS via a presynaptic mechanism. These actions result in the inhibition of synaptic transmission and could play a role in the autonomic responses to hypoxia