Establishment and opertion of a hospital pyrogen assay program.
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Animals↗
Biomedical subjects
C N May
Publications and source records attributed to C N May.
Prepackaging in the pharmacy presents challenges.
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Dosage Forms↗
Salt and water intake and sodium and potassium excretion in spontaneously hypertensive rats.
1. Total fluid and saline intakes were greater in spontaneously hypertensive rats (SHR) than in normotensive rats (NTR). 2. Total fluid and saline intake were significantly elevated in prehypertensive SHR, 5 weeks old, compared with age-matched NTR, and the intakes fell with age in both strains but remained considerably greater in SHR. 3. In SHR, in which the blood pressure was maintained at normotensive levels by treatment with hydralazine, the saline and fluid intakes remained elevated above those of NTR. 4. SHR and NTR fed low sodium diet with water alone to drink have similar excretion rates of sodium, suggesting that their ability to conserve sodium was normal. 5. Measurement of sodium excretion after three different levels of sodium loading, on normal or low sodium diets, also failed to demonstrate an abnormality of renal function in SHR. 6. These results demonstrate that the fluid and saline intakes of SHR are elevated compared with NTR and this difference is independent of the hypertension in SHR and is not secondary to enhanced renal sodium loss.
Aging↗
Prolonged systemic and regional haemodynamic effects of intracerebroventricular angiotensin II in conscious sheep.
1. The haemodynamic mechanisms by which infusion of angiotensin II (AngII), either into the lateral cerebral ventricles (i.c.v.) or intravenously (i.v.), increased arterial pressure were studied in conscious sheep. 2. Sheep were previously fitted with flow probes for measurement of cardiac output and coronary, mesenteric, renal and iliac blood flows. 3. Intracerebroventricular AngII (10 nmol/h for 1 h) increased arterial pressure by 11 +/- 4 mmHg (P < 0.001) due to vasoconstriction, predominantly in the mesentric vasculature. These effects developed over 30 min and took 2 h to return to control. Following the infusion renal conductance increased continuously for 3 h, resulting in a parallel increase in renal blood flow (to 75 +/- 18 mL/min above control, P < 0.001). 4. Intracerebroventricular AngII increased plasma vasopressin from 0.8 +/- 0.3 to 7.2 +/- 1.8 pg/mL (P, 0.01), and reduced plasma renin concentration from 0.9 +/- 0.3 to < 0.4 nmol/L/h. 5. The pressor effect of i.v. AngII (5, 10, 25, 50 nmol/h) also depended on peripheral vasoconstriction, but the pattern of responses was different. The greatest degree of vasoconstriction occurred in the renal, followed by the mesentric and iliac vascular beds; these effects were rapid in onset and offset. 6. In conclusion, the pressor responses to both i.c.v. and i.v. angiotensin depended on peripheral vasoconstriction, but there were contrasting regional haemodynamic changes. ICV AngII caused a prolonged pressor response, mainly due to mesentric vasoconstriction possibly partly due to vasopressin release, and following the infusion there was a pronounced, long-lasting renal vasodilatation. In contrast, i.v. AngII caused vasoconstriction preferentially in the renal vascular bed and its effects were short lasting.
Angiotensin II↗
Functional anatomy of sympathetic premotor cell groups in the medulla.
Pre- and postganglionic sympathetic neurons are organized into discrete functional channels, according to the target they supply. The activity patterns which they show differ between channels, implying that the CNS pathways driving them are not the same. Premotor neurons probably play a key role. This article focuses on what recent evidence tells us about the organization of premotor neurons which control specific sympathetic outflows. Cells that drive muscle vasoconstrictor (MVC), cutaneous vasoconstrictor (CVC), visceral vasoconstrictor (VVC) and renal sympathetic (RSN) outflows have been identified among the premotor neurons of the rostral ventrolateral medulla (RVLM). Other vasomotor, cardiac or adrenal drives are also represented in that cell group. Neurons driving sudomotor responses have been localized in the rostral ventromedial medulla. Evidence on the specific functions of other premotor cell groups is briefly discussed.
Animals↗
The supply of vasomotor drive to individual classes of sympathetic neuron.
The vasoconstrictor supplies to different tissues show distinct patterns of ongoing and reflex activity, indicating that they are driven by distinct central pathways. Vasomotor tone depends heavily on connections from the brainstem, so class-specific vasomotor drives have been sought amongst the sympathetic premotor neurons which provide those connections. Premotor neurons of the rostral ventrolateral medulla (subretrofacial nucleus) provide most descending vasomotor drive. Together, they drive the sympathetic supplies to heart, blood vessels and adrenal, but not 'non-cardiovascular' sympathetic responses (sweating, pupil dilatation, piloerection, etc.). Individually, they provide preferential or selective drives to particular classes of 'cardiovascular' sympathetic outflow. Subretrofacial neurons are arranged topographically, forming a neural map of the functional class (target tissue), not the body region, of the driven outflows. It is still unknown whether other premotor cell groups are organised this way. Nor are the premotor pathways to 'non-cardiovascular' sympathetic nerves yet well-defined.
Animals↗
Chemical synthesis of an O-phosphorylated tyrosine analogue of human angiotensin II, [Tyr(P)4] angiotensin II, and its vasoconstrictor effect in intact sheep.
The derivative N alpha-fluorenylmethoxy-carbonyl-O-dimethylphosphono-L-tyrosi ne was utilized in continuous-flow solid-phase synthesis to prepare the O-phosphotyrosine analogue of human angiotensin II, [Tyr(P)4] angiotensin II. Side-chain deprotection, including the removal of the methyl phosphate groups, as well as cleavage of the peptide from the solid support was achieved with 1 M trimethylsilyl-bromide-thioanisole in trifluoroacetic acid. Overall yield of purified peptide was 46%. The pressor response in intact sheep to graded infusions of the synthetic [Tyr(P)4] angiotensin II showed it to have similar potency to the native angiotensin II. However, a prolonged, elevated mean arterial pressure was observed following cessation of the infusion.
Amino Acid Sequence↗